β cell dedifferentiation, the underlying mechanism of diabetes in Wolfram syndrome.
Kikuko Amo-Shiinoki, Katsuya Tanabe, Wataru Nishimura, Masayuki Hatanaka, Manabu Kondo, Syota Kagawa, Meng Zou, Shuntaro Morikawa, Yoshihiko Sato, Mitsuhisa Komatsu, Hiroki Mizukami, Naoki Nishida, Shun-Ichiro Asahara, Hiroshi Masutani, Yukio Tanizawa
Science translational medicine, 17, 786, eadp2332, 19 Feb. 2025, [International Magazine]
English, Scientific journal, Insulin-dependent diabetes in patients with Wolfram syndrome (WS; OMIM 222300) has been linked to endoplasmic reticulum (ER) stress caused by WFS1 gene mutations. However, the pathological process of ER stress-associated β cell failure remains to be fully elucidated. Our results indicate loss of β cell lineage and subsequent dedifferentiation as the mechanisms underlying functional and mass deficits in WS. An immunohistochemical analysis of human pancreatic sections from deceased individuals with WS revealed a near-complete loss of β cells and subsequent decrease in α cells, suggesting loss of endocrine function. Wfs1-deficient mice displayed dysfunction, gradual loss, and dedifferentiation of β cells, leading to permanent hyperglycemia. Impairment of the β cell lineage was observed after weaning, leading to the mixed phenotype of insulin- and glucagon-producing cells in a subset of the lineage-traced β cells. Islets of Wfs1-deficient mice increased the number of dedifferentiated cells that maintained general endocrine features but were no longer reactive with antisera against pancreatic hormones. Mechanistically, Wfs1-null islets had a lower adenosine triphosphate content and impaired oxidative glycolysis, although mitochondrial oxidative function was maintained. The functional and metabolic alterations of WS β cells were recovered by deletion of thioredoxin-interacting protein (Txnip), an ER stress-induced protein up-regulated in Wfs1 deficiency. Txnip deletion preserved functional β cells and prevented diabetes progression in Wfs1-deficient mice. Together, this study deciphered pathological mechanisms of β cell dedifferentiation in β cell failure and has implications for Txnip inhibition in WS therapy.

Functional Analysis of a Novel HNF4A Variant Identified in a Patient With MODY1
Shuntaro Morikawa, Hui Ling Ko, Ee Chee Ren, Kazuya Hara, Naoya Kaneko, Nozomi Hishimura, Akie Nakamura, Atsushi Manabe
Journal of the Endocrine Society, 8, 6, The Endocrine Society, 06 Apr. 2024
Scientific journal, Abstract

Context

HNF4A–maturity-onset diabetes of the young (MODY1) is a relatively rare subtype of monogenic diabetes caused by loss of function of the HNF4A gene, which encodes the transcription factor HNF4α. HNF4α is known to form heterodimers, and the various combinations of isoforms that make up these heterodimers have been reported to result in a diversity of targeted genes. However, the function of individual HNF4α variant isoforms and the heterodimers comprising both wild-type (WT) and variant HNF4α have not yet been assessed.

Objective

In this study, we analyzed the functional consequence of the HNF4A D248Y variant in vitro.

Methods

We investigated the case of a 12-year-old Japanese girl who developed diabetes at age 11 years. Genetic sequencing detected a novel heterozygous missense HNF4A variant (c.742G > T, p.Asp248Tyr; referred as “D248Y”) in the patient and her relatives who presented with diabetes.

Results

Although the WT HNF4α isoforms (HNF4α2, HNF4α3, HNF4α8, HNF4α9) enhanced the INS gene promoter activity in HepG2 cells, the promoter activity of D248Y was consistently low across all isoforms. The presence of D248Y in homodimers and heterodimers, comprising either HNF4α8 or HNF4α3 or a combination of both isoforms, also reduced the INS promoter activity in Panc-1 cells.

Conclusion

We report the clinical course of a patient with HNF4A-MODY and the functional analysis of novel HNF4A variants, with a focus on the isoforms and heterodimers they form. Our results serve to improve the understanding of the dominant-negative effects of pathogenic HNF4A variants.

Comprehensive overview of disease models for Wolfram syndrome: toward effective treatments.
Shuntaro Morikawa, Katsuya Tanabe, Naoya Kaneko, Nozomi Hishimura, Akie Nakamura
Mammalian genome : official journal of the International Mammalian Genome Society, 13 Feb. 2024, [International Magazine]
English, Scientific journal, Wolfram syndrome (OMIM 222300) is a rare autosomal recessive disease with a devastating array of symptoms, including diabetes mellitus, optic nerve atrophy, diabetes insipidus, hearing loss, and neurological dysfunction. The discovery of the causative gene, WFS1, has propelled research on this disease. However, a comprehensive understanding of the function of WFS1 remains unknown, making the development of effective treatment a pressing challenge. To bridge these knowledge gaps, disease models for Wolfram syndrome are indispensable, and understanding the characteristics of each model is critical. This review will provide a summary of the current knowledge regarding WFS1 function and offer a comprehensive overview of established disease models for Wolfram syndrome, covering animal models such as mice, rats, flies, and zebrafish, along with induced pluripotent stem cell (iPSC)-derived human cellular models. These models replicate key aspects of Wolfram syndrome, contributing to a deeper understanding of its pathogenesis and providing a platform for discovering potential therapeutic approaches.

Adipsic hypernatremia with marked hyperprolactinemia and GH deficiency in a 9-year-old boy.
Hisato Segoe, Akie Nakamura, Kimiaki Uetake, Nozomi Hishimura, Naoya Kaneko, Shuntaro Morikawa, Akari Nakamura-Utsunomiya, Takeshi Yamaguchi
Clinical pediatric endocrinology : case reports and clinical investigations : official journal of the Japanese Society for Pediatric Endocrinology, 33, 3, 163, 168, 2024, [Domestic magazines]
English, Scientific journal, Adipsic hypernatremia is typically caused by congenital dysplasia of the hypothalamus and pituitary or brain tumors. However, cases of adipsic hypernatremia without underlying organic abnormalities are rare, and some cases have been reported to be complicated by hypothalamic-pituitary dysfunction. The patient in this case was a 9-yr-old boy who was referred to our hospital because of hypernatremia. His growth chart revealed that he had rapidly become obese since infancy, with growth retardation since the age of seven. His hands and feet were very cold, and he had erythema on his abdomen, indicating possible autonomic dysregulation due to hypothalamic dysfunction. Several hormone load tests showed severe GH deficiency (GHD) and marked hyperprolactinemia (peak: 302.8 ng/mL). Magnetic resonance imaging revealed no organic abnormalities in the hypothalamus and pituitary gland. GH replacement therapy was initiated. Although his growth rate improved, obesity persisted. To the best of our knowledge, this is the first report of adipsic hypernatremia without organic intracranial abnormalities that was treated with GH. Moreover, the patient's prolactin levels were higher than those reported in previous studies. In conclusion, adipsic hypernatremia requires the evaluation of pituitary function and appropriate therapeutic interventions.

新生児マススクリーニングを契機に発見された先天性甲状腺機能低下症患者のBMIの検討
中村 明枝, 中山 加奈子, 長崎 啓祐, 長谷川 行洋, 鎌崎 穂高, 山口 健史, 森川 俊太郎, 菱村 希, 金子 直哉
日本マス・スクリーニング学会誌, 33, 2, 251, 251, (一社)日本マススクリーニング学会, Aug. 2023
Japanese

Gタンパク共役型受容体101(GPR101)遺伝子変異を同定した複合型下垂体機能低下症の兄弟例
森川 俊太郎, 金子 直哉, 中山 加奈子, 菱村 希, 山口 健史, 佐々木 大輔, 上田 泰弘, 渡邊 さやか, 青柳 勇人, 中村 明枝, 真部 淳
日本内分泌学会雑誌, 99, 1, 311, 311, (一社)日本内分泌学会, May 2023
Japanese

高用量ステロイド吸入により医原性グルココルチコイド過剰および二次性副腎皮質機能不全をきたした女児例
小野 夏実, 金子 直哉, 中山 加奈子, 菱村 希, 山口 健史, 森川 俊太郎, 真部 淳, 中村 明枝
臨床小児医学, 70, 1-6, 57, 63, (財)小児愛育協会, Mar. 2023
Japanese

小児がん経験者(CCS)フォロー中に甲状腺がんを発症した4例
金子 直哉, 菱村 希, 寺下 友佳代, 中山 加奈子, 山口 健史, 森川 俊太郎, 長谷河 昌孝, 澤井 彩織, 杉山 未奈子, 平林 真介, 長 祐子, 真部 淳, 中村 明枝
日本内分泌学会雑誌, 98, 4, 719, 719, (一社)日本内分泌学会, Feb. 2023
Japanese

Palmitoylation couples insulin hypersecretion with β cell failure in diabetes
Guifang Dong, Sangeeta Adak, George Spyropoulos, Qiang Zhang, Chu Feng, Li Yin, Sarah L. Speck, Zeenat Shyr, Shuntaro Morikawa, Rie Asada Kitamura, Rahul S. Kathayat, Bryan C. Dickinson, Xue Wen Ng, David W. Piston, Fumihiko Urano, Maria S. Remedi, Xiaochao Wei, Clay F. Semenkovich
Cell Metabolism, Elsevier BV, Jan. 2023
Scientific journal

The Role of ER Stress in Diabetes: Exploring Pathological Mechanisms Using Wolfram Syndrome
Shuntaro Morikawa, Fumihiko Urano
International Journal of Molecular Sciences, 24, 1, 230, 230, MDPI AG, 23 Dec. 2022
Scientific journal, The endoplasmic reticulum (ER) is a cytosolic organelle that plays an essential role in the folding and processing of new secretory proteins, including insulin. The pathogenesis of diabetes, a group of metabolic disorders caused by dysfunctional insulin secretion (Type 1 diabetes, T1DM) or insulin sensitivity (Type 2 diabetes, T2DM), is known to involve the excess accumulation of “poorly folded proteins”, namely, the induction of pathogenic ER stress in pancreatic β-cells. ER stress is known to contribute to the dysfunction of the insulin-producing pancreatic β-cells. T1DM and T2DM are multifactorial diseases, especially T2DM; both environmental and genetic factors are involved in their pathogenesis, making it difficult to create experimental disease models. In recent years, however, the development of induced pluripotent stem cells (iPSCs) and other regenerative technologies has greatly expanded research capabilities, leading to the development of new candidate therapies. In this review, we will discuss the mechanism by which dysregulated ER stress responses contribute to T2DM pathogenesis. Moreover, we describe new treatment methods targeting protein folding and ER stress pathways with a particular focus on pivotal studies of Wolfram syndrome, a monogenic form of syndromic diabetes caused by pathogenic variants in the WFS1 gene, which also leads to ER dysfunction.

Loss of Function of WFS1 Causes ER Stress-Mediated Inflammation in Pancreatic Beta-Cells.
Shuntaro Morikawa, Lindsey Blacher, Chinyere Onwumere, Fumihiko Urano
Frontiers in endocrinology, 13, 849204, 849204, 2022, [International Magazine]
English, Scientific journal, Wolfram syndrome is a rare genetic disorder characterized by juvenile-onset diabetes mellitus, optic nerve atrophy, hearing loss, diabetes insipidus, and progressive neurodegeneration. Pathogenic variants in the WFS1 gene are the main causes of Wolfram syndrome. WFS1 encodes a transmembrane protein localized to the endoplasmic reticulum (ER) and regulates the unfolded protein response (UPR). Loss of function of WFS1 leads to dysregulation of insulin production and secretion, ER calcium depletion, and cytosolic calpains activation, resulting in activation of apoptotic cascades. Although the terminal UPR has been shown to induce inflammation that accelerates pancreatic β-cell dysfunction and death in diabetes, the contribution of pancreatic β-cell inflammation to the development of diabetes in Wolfram syndrome has not been fully understood. Here we show that WFS1-deficiency enhances the gene expression of pro-inflammatory cytokines and chemokines, leading to cytokine-induced ER-stress and cell death in pancreatic β-cells. PERK and IRE1α pathways mediate high glucose-induced inflammation in a β-cell model of Wolfram syndrome. M1-macrophage infiltration and hypervascularization are seen in the pancreatic islets of Wfs1 whole-body knockout mice, demonstrating that WFS1 regulates anti-inflammatory responses in pancreatic β-cells. Our results indicate that inflammation plays an essential role in the progression of β-cell death and diabetes in Wolfram syndrome. The pathways involved in ER stress-mediated inflammation provide potential therapeutic targets for the treatment of Wolfram syndrome.

A soluble endoplasmic reticulum factor as regenerative therapy for Wolfram syndrome.
Jana Mahadevan, Shuntaro Morikawa, Takuya Yagi, Damien Abreu, Simin Lu, Kohsuke Kanekura, Cris M Brown, Fumihiko Urano
Laboratory investigation; a journal of technical methods and pathology, 100, 9, 1197, 1207, Sep. 2020, [International Magazine]
English, Scientific journal, Endoplasmic reticulum (ER) stress-mediated cell death is an emerging target for human chronic disorders, including neurodegeneration and diabetes. However, there is currently no treatment for preventing ER stress-mediated cell death. Here, we show that mesencephalic astrocyte-derived neurotrophic factor (MANF), a neurotrophic factor secreted from ER stressed cells, prevents ER stress-mediated β cell death and enhances β cell proliferation in cell and mouse models of Wolfram syndrome, a prototype of ER disorders. Our results indicate that molecular pathways regulated by MANF are promising therapeutic targets for regenerative therapy of ER stress-related disorders, including diabetes, retinal degeneration, neurodegeneration, and Wolfram syndrome.

Targeted Next-Generation Sequencing for Congenital Hypothyroidism With Positive Neonatal TSH Screening.
Takeshi Yamaguchi, Akie Nakamura, Kanako Nakayama, Nozomi Hishimura, Shuntaro Morikawa, Katsura Ishizu, Toshihiro Tajima
The Journal of clinical endocrinology and metabolism, 105, 8, 01 Aug. 2020, [International Magazine]
English, Scientific journal, PURPOSE: Congenital hypothyroidism (CH) is the most common neonatal endocrine disorder; however, its molecular etiology remains poorly understood. METHODS: We performed genetic analysis of 24 causative genes using next-generation sequencing in 167 CH cases, comprising 57 dyshormonogenesis (DH), 32 dysgenesis (TD) and 78 undiagnosed. The pathogenicity of variants was assessed by the American College of Medical Genetics guidelines, inheritance pattern, and published evidence. Furthermore, we compared the oligogenic groups and monogenic groups to examine the correlation between variant dosage and severity. RESULTS: We identified variants in 66.5% cases (111/167) and 15 genes, DUOX2, TSHR, PAX8, TG, TPO, DUOXA2, JAG1, GLIS3, DUOX1, IYD, SLC26A4, SLC5A5, SECISBP2, DIO1, and DIO3. Biallelic variants were identified in 12.6% (21/167), oligogenic in 18.0% (30/167), and monogenic in 35.9% (60/167); however, 68.5% of variants were classified as variant of unknown significance (VUS). Further examinations showed that 3 out of 32 cases with TD (9.4%) had pathogenic variants (2 of TSHR and 1 of TPO), and 8 out of 57 cases with DH (14.0%) (7 of DUOX2, 1 of TG) had pathogenic variants. In addition, TSH levels at the first visit were significantly higher in the oligogenic group than in the monogenic group. CONCLUSIONS: The detection rate of pathogenic variants in Japanese CH was similar to that previously reported. Moreover, oligogenic cases were likely to be more severe than monogenic cases, suggesting that CH may exhibit a gene dosage effect. Further analysis of VUS pathogenicity is required to clarify the molecular basis of CH.

Gene-edited human stem cell-derived β cells from a patient with monogenic diabetes reverse preexisting diabetes in mice.
Kristina G Maxwell, Punn Augsornworawat, Leonardo Velazco-Cruz, Michelle H Kim, Rie Asada, Nathaniel J Hogrebe, Shuntaro Morikawa, Fumihiko Urano, Jeffrey R Millman
Science translational medicine, 12, 540, 22 Apr. 2020, [International Magazine]
English, Scientific journal, Differentiation of insulin-producing pancreatic β cells from induced pluripotent stem cells (iPSCs) derived from patients with diabetes promises to provide autologous cells for diabetes cell replacement therapy. However, current approaches produce patient iPSC-derived β (SC-β) cells with poor function in vitro and in vivo. Here, we used CRISPR-Cas9 to correct a diabetes-causing pathogenic variant in Wolfram syndrome 1 (WFS1) in iPSCs derived from a patient with Wolfram syndrome (WS). After differentiation to β cells with our recent six-stage differentiation strategy, corrected WS SC-β cells performed robust dynamic insulin secretion in vitro in response to glucose and reversed preexisting streptozocin-induced diabetes after transplantation into mice. Single-cell transcriptomics showed that corrected SC-β cells displayed increased insulin and decreased expression of genes associated with endoplasmic reticulum stress. CRISPR-Cas9 correction of a diabetes-inducing gene variant thus allows for robust differentiation of autologous SC-β cells that can reverse severe diabetes in an animal model.

Hypoglycemia in type 1A diabetes can develop before insulin therapy: A retrospective cohort study.
Takeshi Yamaguchi, Rumi Hachiya, Sayaka Watanabe-Yamamoto, Kentaro Sawano, Shuntaro Morikawa, Akie Nakamura, Yukihiro Hasegawa
Diabetes research and clinical practice, 147, 87, 92, Jan. 2019, [International Magazine]
English, Scientific journal, AIMS: There are as yet no cohort studies of hypoglycemia in type 1 diabetes before starting insulin therapy. Our aim was to determine the frequency and clinical features of hypoglycemia in patients with type 1A diabetes prior to commencing insulin therapy. METHODS: Eighty-seven patients with type 1A diabetes were enrolled, and a retrospective chart review of the patients was conducted. RESULTS: Hypoglycemia before insulin therapy occurred in six of 87 patients (6.9%). The HbA1c levels at the diagnosis of type 1A diabetes in the hypoglycemia group were lower than in the non-hypoglycemia group (median: 7.3% (56 mmol/mol) vs. 11.9% (106 mmol/mol), p < 0.0001). Similarly, the 24-hour urinary C-peptide (UCPR) levels of the former group were higher than those of the latter group (16.5 μg/day/m2 vs. 7.0 μg/day/m2, p = 0.0075). Hypoglycemic episodes occurred mostly in the postprandial period and gradually disappeared with a decrease in insulin secretion. CONCLUSIONS: We demonstrated that some patients with type 1A diabetes experience hypoglycemic episodes before insulin therapy. Patients with early-stage type 1A diabetes with relatively low HbA1c or high UCPR have a risk of hypoglycemia. These findings may impact when and how insulin is introduced in the treatment of early-stage type 1A diabetes.

(Epi)genetic defects of MKRN3 are rare in Asian patients with central precocious puberty.
Erina Suzuki, Hirohito Shima, Masayo Kagami, Shun Soneda, Toshiaki Tanaka, Shuichi Yatsuga, Junko Nishioka, Yuji Oto, Toshiya Kamiya, Yasuhiro Naiki, Tsutomu Ogata, Yasuko Fujisawa, Akie Nakamura, Sayaka Kawashima, Shuntaro Morikawa, Reiko Horikawa, Shinichiro Sano, Maki Fukami
Human genome variation, 6, 7, 7, 2019, [International Magazine]
English, We sequenced MKRN3, the major causative gene of central precocious puberty in Western countries, in 24 Japanese or Chinese patients and examined the DNA methylation and copy-number statuses of this gene in 19 patients. We identified no (epi)genetic defects except for one previously reported mutation. These results, together with reports from Korea, indicate that MKRN3 defects are rare in Asian populations. The ethnic differences likely reflect Western country-specific founder mutations and the rarity of de novo mutations.

A Japanese patient with congenital central hypothyroidism caused by a novel IGSF1 mutation.
Takeshi Yamaguchi, Tomoyuki Hothubo, Shuntaro Morikawa, Akie Nakamura, Toshihiko Mori, Toshihiro Tajima
Journal of pediatric endocrinology & metabolism : JPEM, 31, 3, 355, 359, 28 Mar. 2018, [International Magazine]
English, BACKGROUND: IGSF1 abnormality causes diverse symptoms, including congenital central hypothyroidism (CCH), prolactin hyposecretion, testicular enlargement and delayed puberty. CASE PRESENTATION: Here, we report a case of a male patient who visited our hospital with a chief complaint of abdominal pain and short stature, in whom we identified a novel IGSF1 mutation. He was closely examined because of chronic constipation since infancy, persistent abdominal pain at 14 years of age and marked short stature (-4.7 standard deviation [SD] for normal Japanese boys). He was diagnosed with CCH. Decreased prolactin (PRL) secretion was also observed. IGSF1 analysis revealed a novel mutation at the splicing donor site (c.2065+1G>A) in intron 11. In silico analysis predicted this mutation to be a non-functional splice donor site. After thyroid hormone replacement, his thyroid function, constipation and growth rate improved. CONCLUSIONS: This is the first report of a patient in whom constipation and short stature led to a diagnosis of CCH with a novel IGSF1 mutation.

Two siblings with congenital central hypothyroidism caused by a novel mutation in the IGSF1 gene.
Makiko Oguma, Mizuki Kobayashi, Masayo Yamazaki, Koji Yokoyama, Shuntaro Morikawa, Takeshi Yamaguchi, Takanori Yamagata, Toshihiro Tajima
Clinical pediatric endocrinology : case reports and clinical investigations : official journal of the Japanese Society for Pediatric Endocrinology, 27, 2, 95, 100, 2018, [Domestic magazines]
English, Scientific journal, Genetic defects in the immunoglobulin superfamily member 1(IGSF1) protein are the cause of congenital central hypothyroidism (C-CH). Here we report two Japanese siblings with C-CH due to a novel IGSF1 mutation. The youngest brother showed a failure to thrive, hypothermia, and neonatal icterus six days after birth. Further endocrine evaluations led to the diagnosis of C-CH. In addition, PRL deficiency was later detected. In contrast, the elder brother did not show symptoms of severe hypothyroidism during the neonatal period, but he had been followed up by doctors due to psychomotor developmental delays since the age of 1 yr. At the age of 3 yr, he had low thyroxine and PRL levels and was also diagnosed with C-CH. Because of the C-CH and PRL deficiency, an IGSF1 deficiency was suspected. Sequence analysis of the IGSF1 gene identified a novel hemizygous mutation of p.Trp1173GlyfsTer8 (NM_001170961.1:c.3517del) in both siblings. In conclusion, the phenotypic severity of C-CH is different, even in siblings. Importantly, an IGSF1 deficiency may result in severe hypothyroidism during the neonatal period.

Four Japanese Patients with Congenital Nephrogenic Diabetes Insipidus due to the AVPR2 Mutations.
Noriko Namatame-Ohta, Shuntaro Morikawa, Akie Nakamura, Kumihiro Matsuo, Masahide Nakajima, Kazuhiro Tomizawa, Yusuke Tanahashi, Toshihiro Tajima
Case reports in pediatrics, 2018, 6561952, 6561952, 2018, [International Magazine]
English, Almost 90% of nephrogenic diabetes insipidus (NDI) is caused by mutations in the arginine vasopressin receptor 2 gene (AVPR2) on the X chromosome. Herein, we reported clinical and biochemical parameters in four cases of three unrelated Japanese families and analyzed the status of the AVPR2. Two of the four patients had poor weight gain. However, in the male and female sibling cases, neither had poor weight gain while toddlers, but in the male sibling, episodes of recurrent fever, polyuria, and polydipsia led to the diagnosis of NDI at 4 years of age. Analysis of AVPR2 identified two nonsense mutations (c.299_300insA; p.K100KfsX91 and c.296G > A; p.W99X) and one missense mutation (c.316C > T; p.R106C). These mutations were previously reported. The patient with c.316C > T; p.R106C had milder symptoms consistent with previous reports. Of the familial cases, the sister was diagnosed as having NDI, but a skewed X-inactivation pattern in her peripheral blood lymphocytes was not identified. In conclusion, our study expands the spectrum of phenotypes and characterized mutations in AVPR2 in NDI.

A novel heterozygous mutation of the WFS1 gene leading to constitutive endoplasmic reticulum stress is the cause of Wolfram syndrome.
Shuntaro Morikawa, Toshihiro Tajima, Akie Nakamura, Katsura Ishizu, Tadashi Ariga
Pediatric diabetes, 18, 8, 934, 941, Dec. 2017, [International Magazine]
English, Scientific journal, BACKGROUND: Wolfram syndrome (WS) is a disorder characterized by the association of insulin-dependent diabetes mellitus (DM), diabetes insipidus, deafness, and optic nerve atrophy. WS is caused by WFS1 mutations encoding WFS1 protein expressed in endoplasmic reticulum (ER). During ER protein synthesis, misfolded and unfolded proteins accumulate, known as "ER stress". This is attenuated by the unfolded protein response (UPR), which recovers and maintains ER functions. Because WFS1 is a UPR component, mutant WFS1 might cause unresolvable ER stress conditions and cell apoptosis, the major causes underlying WS symptoms. We encountered an 11-month-old Japanese female WS patient with insulin-dependent DM, congenital cataract and severe bilateral hearing loss. OBJECTIVE: Analyze the WFS1 and functional consequence of the patient WFS1 in vitro. RESULTS: The patient WFS1 contained a heterozygous 4 amino acid in-frame deletion (p.N325_I328del). Her mutant WFS1 increased GRP78 and ATF6α promoter activities in the absence of thapsigargin, indicating constitutive ER stress and nuclear factor of activated T-cell reporter activity, reflecting elevated cytosolic Ca2+ signals. Mutant transfection into cells reduced mRNA expression levels of sarcoplasmic/endoplasmic reticulum Ca2+ transport ATPase 2b (SERCA2b) compared with wild type. Because SERCA2b is required for ER and cytoplasmic Ca2+ homeostasis, decreased SERCA2b expression might affect ER Ca2+ efflux, causing cell apoptosis. CONCLUSION: A novel heterozygous mutation of WFS1 induced constitutive ER stress through ATF6α activation and ER Ca2+ efflux, resulting in cell apoptosis. These results provide new insights into the roles of WFS1 in UPR and mechanism of monogenic DM.

CLINICAL FEATURES OF TWO JAPANESE PATIENTS WITH MICRODUPLICATIONS OF 5Q35.2-Q35.3 ENCOMPASSING NSD1
Sayaka Yamamoto, Akie Nakamura, Hayato Aoyagi, Satoru Shida, Yasuhiro Ueda, Takeshi Yamaguchi, Shuntaro Morikawa, Katsura Ishizu, Masayo Kagami, Maki Fukami, Toshihiro Tajima
HORMONE RESEARCH IN PAEDIATRICS, 88, 382, 382, 2017, [Peer-reviewed]
English

Clinical features and molecular basis of pseudohypoaldosteronism type 1.
Toshihiro Tajima, Shuntaro Morikawa, Akie Nakamura
Clinical pediatric endocrinology : case reports and clinical investigations : official journal of the Japanese Society for Pediatric Endocrinology, 26, 3, 109, 117, 2017, [Domestic magazines]
English, Scientific journal, Pseudohypoaldosteronism (PHA) type 1 is a disease showing mineralocorticoid resistance in the kidney and/or other mineralocorticoid target tissues. Patients with PHA1 present very high plasma aldosterone and renin levels, but they develop excessive salt wasting. There are three types of PHA1. The systemic form of PHA1 is inherited in an autosomal recessive manner and causes severe life-long salt loss in multiple target tissues, such as sweat glands, salivary glands, the colonic epithelium, and the lung. In the systemic form of PHA1, life-long salt supplementation is necessary. The second type is the renal form, where aldosterone resistance is shown only in the kidney, and its inheritance is autosomal dominant. In the renal form of PHA1, salt supplementation generally becomes unnecessary by 1-3 yr of age. The third type is the secondary PHA1, which is strongly associated with urinary tract infections and/or urinary tract malformations. This review summarizes the clinical features and molecular basis of PHA1. Understanding of its pathogenesis can be helpful for the early diagnosis and clinical care of affected children with PHA1.

A Japanese Family with Central Hypothyroidism Caused by a Novel IGSF1 Mutation.
Satsuki Nishigaki, Takashi Hamazaki, Keinosuke Fujita, Shuntaro Morikawa, Toshihiro Tajima, Haruo Shintaku
Thyroid : official journal of the American Thyroid Association, 26, 12, 1701, 1705, Dec. 2016, [International Magazine]
English, Scientific journal, BACKGROUND: Hemizygous mutations in the immunoglobulin superfamily member 1 (IGSF1) gene have been demonstrated to cause congenital central hypothyroidism in males. This study reports a family with a novel mutation in the IGSF1 gene located on the long arm of the X chromosome. PATIENT FINDINGS: A two-month-old boy was diagnosed with central hypothyroidism because of prolonged jaundice. A thyrotropin-releasing hormone (TRH) stimulation test indicated dysfunction in both the hypothalamus and the pituitary gland, and prompted the IGSF1 gene to be analyzed. The patient had a novel nonsense variant, c.2713C>T (p.Q905X), in exon 14 of the IGSF1 gene. Studies of the family revealed that the patient's sister and mother were heterozygous carriers of the IGSF1 mutation. The patient's maternal uncle carried the same mutation as the proband but had no overt symptoms. The mother and uncle started levothyroxine supplementation because of subclinical hypothyroidism. SUMMARY: A novel mutation (c.2713C>T, p.Q905X) of the IGSF1 gene was identified that causes congenital central hypothyroidism in a Japanese family. The findings further expand the clinical heterogeneity of this entity.

Spondyloepiphyseal dysplasia congenita caused by double heterozygous mutations in COL2A1.
Osamu Kawano, Akie Nakamura, Shuntaro Morikawa, Kimiaki Uetake, Katsura Ishizu, Toshihiro Tajima
American journal of medical genetics. Part A, 167, 7, 1578, 81, Jul. 2015, [International Magazine]
English, Scientific journal, Spondyloepiphyseal dysplasia congenita (SEDC) is a group of rare inherited chondrodysplasias characterized by short stature, abnormal epiphyses, and flattened vertebral bodies. SEDC is usually caused by substitution of glycine residue with another amino acid in the triple helical domains of alpha 1 chains, which consist of type II collagen (COL2A1). Herein, we describe a unique case of SEDC with mild coxa vara (SEDC-M) caused by double de novo COL2A1 mutations located on the same allele. One mutation, p.G504S, was previously described in patients with SEDC, whereas the other, p.G612A, was a novel mutation; both were located in the triple helical domain. Neither mutation was identified in the parents and appeared to be de novo. To the best of our knowledge, this is the first study involving a patient with a type II collagenopathy with two COL2A1 mutations on the same allele. The case was characterized by a more severe phenotype compared with previously reported cases involving a single p.G504S mutation, which may have been the result of the double mutation.

Two Japanese patients with the renal form of pseudohypoaldosteronism type 1 caused by mutations of NR3C2.
Shuntaro Morikawa, Nagisa Komatsu, Sonoko Sakata, Akari Nakamura-Utsunomiya, Satoshi Okada, Toshihiro Tajima
Clinical pediatric endocrinology : case reports and clinical investigations : official journal of the Japanese Society for Pediatric Endocrinology, 24, 3, 135, 8, Jul. 2015, [Domestic magazines]
English, Pseudohypoaldosteronism type 1 (PHA1) is a disease characterized by neonatal salt loss due to aldosterone resistance. Two types of PHA1 are known: an autosomal recessive systemic form and an autosomal dominant renal form. The cause of the renal form of PHA1 is heterozygous mutations in NR3C2, which encodes the mineralocorticoid receptor (MR). We encountered two female Japanese infants with the renal form of PHA1 and analyzed NR3C2. The two patients had poor weight gain, and one was developmentally delayed. Genetic analysis identified one novel mutation (c.492_493insTT, p.Met166LeufsX8) and one previously reported mutation (p.R861X). The two produced a premature stop codon, resulting in haploinsufficiency of the MR. In conclusion, genetic analysis of NR3C2 is useful for diagnosis and planning therapeutic strategies.

Two heterozygous mutations of the AMH gene in a Japanese patient with persistent Müllerian duct syndrome.
Shuntaro Morikawa, Kimihiko Moriya, Katsura Ishizu, Toshihiro Tajima
Journal of pediatric endocrinology & metabolism : JPEM, 27, 11-12, 1223, 6, Nov. 2014, [International Magazine]
English, Scientific journal, Persistent Müllerian duct syndrome (PMDS) is an autosomal recessive disorder of sex development (DSD) characterized by the presence of Müllerian duct derivatives in 46, XY phenotypic males. To date, more than 50 different mutations of the anti-Müllerian hormone gene (AMH) have been reported. Here, we report two novel mutations of AMH in a Japanese patient with PMDS. A 1-year-old male presented with bilateral cryptorchidism and normal male external genitalia. A laparoscopic surgery revealed a uterus and fallopian tubes. Serum AMH was very low. The patient's elder brother was also diagnosed as having PMDS at another hospital. Genetic analysis of AMH showed two novel mutations of p.N486T and p.V527L. Given that these two amino acids are well conserved among different species of AMH, the substitution of two amino acids might affect the normal function of AMH. In conclusion, PMDS should be included in differential diagnoses of cryptorchidism.

Neonatal screening and a new cause of congenital central hypothyroidism.
Toshihiro Tajima, Akie Nakamura, Shuntaro Morikawa, Katsura Ishizu
Annals of pediatric endocrinology & metabolism, 19, 3, 117, 21, Sep. 2014, [International Magazine]
English, Scientific journal, Congenital central hypothyroidism (C-CH) is a rare disease in which thyroid hormone deficiency is caused by insufficient thyrotropin (TSH) stimulation of a normally-located thyroid gland. Most patients with C-CH have low free thyroxine levels and inappropriately low or normal TSH levels, although a few have slightly elevated TSH levels. Autosomal recessive TSH deficiency and thyrotropin-releasing hormone receptor-inactivating mutations are known to be genetic causes of C-CH presenting in the absence of other syndromes. Recently, deficiency of the immunoglobulin superfamily member 1 (IGSF1) has also been demonstrated to cause C-CH. IGSF1 is a plasma membrane glycoprotein highly expressed in the pituitary. Its physiological role in humans remains unknown. IGSF1 deficiency causes TSH deficiency, leading to hypothyroidism. In addition, approximately 60% of patients also suffer a prolactin deficiency. Moreover, macroorchidism and delayed puberty are characteristic features. Thus, although the precise pathophysiology of IGSF1 deficiency is not established, IGSF1 is considered to be a new factor controlling growth and puberty in children.

A Japanese family with nonautoimmune hyperthyroidism caused by a novel heterozygous thyrotropin receptor gene mutation.
Akie Nakamura, Shuntaro Morikawa, Hayato Aoyagi, Katsura Ishizu, Toshihiro Tajima
Pediatric research, 75, 6, 749, 53, Jun. 2014, [International Magazine]
English, Scientific journal, BACKGROUND: Hyperthyroidism caused by activating mutations of the thyrotropin receptor gene (TSHR) is rare in the pediatric population. METHODS: We found a Japanese family with hyperthyroidism without autoantibody. DNA sequence analysis of TSHR was undertaken in this family. The functional consequences for the Gs-adenylyl cyclase and Gq/11-phospholipase C signaling pathways and cell surface expression of receptors were determined in vitro using transiently transfected human embryonic kidney 293 cells. RESULTS: We identified a heterozygous mutation (M453R) in exon 10 of TSHR. In this family, this mutation was found in all individuals who exhibited hyperthyroidism. The results showed that this mutation resulted in constitutive activation of the Gs-adenylyl cyclase system. However, this mutation also caused a reduction in the activation capacity of the Gq/11-phospholipase C pathway, compared with the wild type. CONCLUSION: We demonstrate that the M453R mutation is the cause of nonautoimmune hyperthyroidism.

Results from 28 years of newborn screening for congenital adrenal hyperplasia in sapporo.
Shuntaro Morikawa, Akie Nakamura, Kaori Fujikura, Masaru Fukushi, Tomoyuki Hotsubo, Jun Miyata, Katsura Ishizu, Toshihiro Tajima
Clinical pediatric endocrinology : case reports and clinical investigations : official journal of the Japanese Society for Pediatric Endocrinology, 23, 2, 35, 43, Apr. 2014, [Domestic magazines]
English, Scientific journal, The primary goal of newborn mass screening (MS) for congenital adrenal hyperplasia (CAH) is the prevention of life-threatening salt-wasting crisis in the most severe forms of CAH, and MS for CAH has been implemented in several countries. We summarize here our experience and results from newborn CAH MS from 1982 to 2010 in Sapporo City. During these 28 yr, the level of 17-hydroxyprogesterone (17-OHP) was determined in MS of samples from 498,147 newborns. During this period, 26 individuals (19 females and 7 males) with 21-hydroxylase deficiency (21-OHD) were detected. Of the 26 CAH, 20 were classified as having the salt-wasting (SW) form, 4 were classified as having the simple virilizing (SV) form, and 2 were classified as having the noncalssic (NC) form. Therefore, the frequency of the classical type of CAH was 1 in 20,756. In order to improve the effectiveness, we employed high-performance liquid chromatography (HPLC) as a second tier test from 2000. During this period, among the recalled babies, 75.4% were born prior to the 37th wk of gestation age, and the recall rate was 5.38% for premature neonates and 0.06% for mature neonates. MS for CAH in Sapporo is effective for the identification of the SW and SV forms of 21-OHD. However, the recall rate of premature babies is still high after the introduction of HPLC as a second tier test.

A case of recurrent rhabdomyolysis associated with childhood Sjögren’s syndrome
Shuntaro Morikawa, Ichiro Kobayashi, Yutaka Uzuki, Masahiro Ueki, Tetsuo Hattori, Hayato Aoyagi
OJPed, 03, 03, 276, 278, Scientific Research Publishing, Inc,, 2013, [Peer-reviewed]
Scientific journal

オクトレオチド持続皮下注を要したが4年後にジアゾキサイド内服へ変更できた先天性高インスリン血症の一例
中山 加奈子, 菱村 希, 山口 健史, 森川 俊太郎, 石津 桂, 依藤 亨, 田島 敏弘, 中村 明枝, 日本内分泌学会雑誌, 95, 1, 351, 351, Apr. 2019
(一社)日本内分泌学会, Japanese

オクトレオチド持続皮下注を要したが4年後にジアゾキサイド内服へ変更できた先天性高インスリン血症の一例
中山 加奈子, 菱村 希, 山口 健史, 森川 俊太郎, 石津 桂, 依藤 亨, 田島 敏弘, 中村 明枝, 日本内分泌学会雑誌, 95, 1, 379, 379, Apr. 2019
(一社)日本内分泌学会, Japanese

1A型糖尿病におけるインスリン治療開始前の低血糖 後方視的観察研究　　　　　　　　　　　　　　　
蜂屋 瑠見, 山口 健史, 渡邊 さやか, 澤野 堅太郎, 森川 俊太郎, 中村 明枝, 長谷川 行洋, 糖尿病, 62, Suppl.1, S, 286, Apr. 2019
(一社)日本糖尿病学会, Japanese

副腎アンドロゲン産生腫瘍摘出術後に中枢性思春期早発症を発症した女児例
山本 さやか, 山口 健史, 森川 俊太郎, 本多 昌平, 中村 明枝, 日本内分泌学会雑誌, 94, 1, 276, 276, Apr. 2018
(一社)日本内分泌学会, Japanese

インスリン治療開始前に低血糖を認めた1A型糖尿病6例の検討
山口 健史, 蜂屋 瑠見, 山本 さやか, 森川 俊太郎, 中村 明枝, 長谷川 行洋, 日本内分泌学会雑誌, 94, 1, 334, 334, Apr. 2018
(一社)日本内分泌学会, Japanese

新生児マススクリーニングで発見された非古典型21-水酸化酵素欠損症の長期経過
田島 敏広, 中村 明枝, 森川 俊太郎, 山口 健史, 日本内分泌学会雑誌, 93, 4, 1295, 1295, Dec. 2017
(一社)日本内分泌学会, Japanese

当科で経験したバセドウ病3例の発症から臨床経過　　　　　　　　　　　　　　　
信田 大喜子, 上野 倫彦, 木村 修平, 辻岡 孝郎, 内田 雅也, 森川 俊太郎, 日本小児科学会雑誌, 121, 11, 1885, 1885, Nov. 2017
(公社)日本小児科学会, Japanese

学校心臓検診を契機に発見されたバセドウ病の2女児例　　　　　　　　　　　　　　　
内藤 広行, 伊東 広臨, 中本 哲, 小西 祥平, 森川 俊太郎, 石津 桂, 市立千歳市民病院医誌, 13, 1, 4, 6, Oct. 2017
市立千歳市民病院, Japanese

男性化徴候を契機に診断された機能性副腎腺腫の一例
坂本 沙織, 本多 昌平, 宮城 久之, 湊 雅嗣, 鈴木 麻由, 中村 明枝, 森川 俊太郎, 山口 健史, 武冨 紹信, 日本小児血液・がん学会雑誌, 54, 4, 327, 327, Oct. 2017
(一社)日本小児血液・がん学会, Japanese

新生児マススクリーニングを契機に診断された非古典型21水酸化酵素欠損症女児の臨床経過
森川 俊太郎, 山口 健史, 石津 桂, 本間 桂子, 長谷川 奉延, 田島 敏広, 中村 明枝, 日本マス・スクリーニング学会誌, 27, 2, 204, 204, Jul. 2017
(一社)日本マススクリーニング学会, Japanese

新生児マス・スクリーニングで発見された甲状腺ホルモン不応症の1例
山口 健史, 森川 俊太郎, 石津 桂, 臼井 健, 田島 敏広, 日本マス・スクリーニング学会誌, 27, 1, 59, 62, May 2017
(一社)日本マススクリーニング学会, Japanese

テストステロン上昇を認め、アレイCGHでNR5A1を含む2.2Mbの欠失が判明した46、XY DSDの1例
山口 健史, 田島 敏広, 森川 俊太郎, 石津 桂, 中村 明枝, 五十嵐 麻希, 深見 真紀, 日本内分泌学会雑誌, 93, 1, 308, 308, Apr. 2017
(一社)日本内分泌学会, Japanese

血糖コントロールに難渋しているインスリン抗体陽性1型糖尿病の女児例　　　　　　　　　　　　　　　
森川 俊太郎, 山口 健史, 石津 桂, 菱村 希, 寺田 健作, 信田 大喜子, 上野 倫彦, 田島 敏広, 有賀 正, 日本小児科学会雑誌, 121, 2, 295, 295, Feb. 2017
(公社)日本小児科学会, Japanese

SPONTANEOUS POSTPRANDIAL HYPOGLYCEMIA BEFORE INSULIN INTRODUCTION IN EARLY-STAGE TYPE 1A DIABETES MELLITUS
Rumi Hachiya, Takeshi Yamaguchi, Shuntaro Morikawa, Akie Nakamura, Katsura Ishizu, Yukihiro Hasegawa, HORMONE RESEARCH IN PAEDIATRICS, 88, 618, 618, 2017
English, Summary international conference

テストステロン上昇を認め、アレイCGHでNR5A1を含む2.2Mbの欠失を同定した46,XY DSDの1例
田島 敏広, 山口 健史, 森川 俊太郎, 石津 桂, 中村 明枝, 五十嵐 麻希, 深見 真紀, 日本内分泌学会雑誌, 92, 3, 800, 800, Jan. 2017
(一社)日本内分泌学会, Japanese

当科における成人成長ホルモン分泌不全症38症例の検討
石津 桂, 山口 健史, 森川 俊太郎, 田島 敏広, 有賀 正, 日本内分泌学会雑誌, 92, S.Branc, 11, 11, Dec. 2016
(一社)日本内分泌学会, Japanese

Wolfram症候群における成長障害メカニズムの解明 小胞体ストレスによるGH分泌への影響　　　　　　　　　　　　　　　
森川 俊太郎, 山口 健史, 石津 桂, 有賀 正, 田島 敏広, 中村 明枝, 成長科学協会研究年報, 39, 139, 146, Sep. 2016
(公財)成長科学協会, Japanese

TSH、FT4同時測定による新生児マス・スクリーニングで発見された甲状腺ホルモン不応症の2例
山口 健史, 森川 俊太郎, 石津 桂, 臼井 健, 田島 敏広, 日本マス・スクリーニング学会誌, 26, 2, 204, 204, Jul. 2016
(一社)日本マススクリーニング学会, Japanese

父由来アリルに新規ABCC8遺伝子異常を同定した先天性高インスリン性低血糖症の1例　　　　　　　　　　　　　　　
森川 俊太郎, 國崎 純, 母坪 智行, 森 俊彦, 石津 桂, 田島 敏広, 日本小児科学会雑誌, 120, 5, 920, 920, May 2016
(公社)日本小児科学会, Japanese

恒常的な小胞体ストレスにより、重症Wolfram症候群を発症する新規WFS1遺伝子変異の病態解明
森川 俊太郎, 中村 明枝, 石津 桂, 田島 敏広, 日本内分泌学会雑誌, 92, 1, 201, 201, Apr. 2016
(一社)日本内分泌学会, Japanese

脊椎骨端異形成症(Spondylometaphyseal dysplasia)Kozlowski type女児の1例
田島 敏広, 森川 俊太郎, 石津 桂, 西村 玄, 日本内分泌学会雑誌, 92, 1, 250, 250, Apr. 2016
(一社)日本内分泌学会, Japanese

器質的疾患により思春期早発症を来した2例　　　　　　　　　　　　　　　
山口 健史, 森川 俊太郎, 石津 桂, 江川 潔, 白石 秀明, 田島 敏広, 有賀 正, 日本小児科学会雑誌, 120, 2, 346, 346, Feb. 2016
(公社)日本小児科学会, Japanese

脊椎骨端異形成症(spondylometaphyseal dysplasia)Kozlowski type女児の1例　　　　　　　　　　　　　　　
森川 俊太郎, 石津 桂, 田島 敏広, 有賀 正, 西村 玄, 日本小児科学会雑誌, 120, 2, 347, 347, Feb. 2016
(公社)日本小児科学会, Japanese

当科における成人GHDへのトランジション38症例の検討
石津 桂, 森川 俊太郎, 田島 敏広, 日本内分泌学会雑誌, 91, 3, 843, 843, Oct. 2015
(一社)日本内分泌学会, Japanese

NR5A1遺伝子に新規遺伝子変異を同定した46,XY性分化疾患の1例
田島 敏広, 石津 桂, 森川 俊太郎, 日本内分泌学会雑誌, 91, 2, 567, 567, Sep. 2015
(一社)日本内分泌学会, Japanese

IGSF1遺伝子変異により先天性中枢性甲状腺機能低下症を引き起こす病態の解明　　　　　　　　　　　　　　　
森川 俊太郎, 田島 敏広, 母坪 智行, 成長科学協会研究年報, 38, 169, 173, Aug. 2015
(公財)成長科学協会, Japanese

新生児マス・スクリーニング検査でみつかったTPO異常症の2例
石津 桂, 森川 俊太郎, 鳴海 覚志, 長谷川 奉延, 田島 敏広, 日本マス・スクリーニング学会誌, 25, 2, 227, 227, Jul. 2015
(一社)日本マススクリーニング学会, Japanese

札幌市における先天性甲状腺機能低下症マススクリーニング2005-2012年の成績
田島 敏広, 森川 俊太郎, 石津 桂, 山岸 卓弥, 藤倉 かおり, 田上 泰子, 花井 潤師, 宮田 淳, 日本マス・スクリーニング学会誌, 25, 2, 230, 230, Jul. 2015
(一社)日本マススクリーニング学会, Japanese

Constant Increase of ER Stress Caused by a Novel Heterozygous Mutation of WFS1 Gene
Shuntaro Morikawa, Akie Nakamura, Katsura Ishizu, Toshihiro Tajima, DIABETES, 64, A582, A582, Jun. 2015
English, Summary international conference

先天性甲状腺疾患の基礎と臨床 先天性中枢性甲状腺機能低下症の新たな病態について
中村 明枝, 森川 俊太郎, 石津 桂, 田島 敏広, 日本内分泌学会雑誌, 91, 1, 182, 182, Apr. 2015
(一社)日本内分泌学会, Japanese

札幌市における先天性甲状腺機能低下症マススクリーニング 2005-2012年の成績
森川 俊太郎, 田島 敏広, 石津 桂, 中村 明枝, 藤倉 かおり, 福士 勝, 日本内分泌学会雑誌, 91, 1, 306, 306, Apr. 2015
(一社)日本内分泌学会, Japanese

恒常的小胞体ストレスを誘導する新規WFS1遺伝子変異に伴った重症Wolfram症候群の女児例
森川 俊太郎, 中村 明枝, 石津 桂, 久間木 悟, 田島 敏広, 日本内分泌学会雑誌, 91, 1, 369, 369, Apr. 2015
(一社)日本内分泌学会, Japanese

COL2A1遺伝子の同一アレル上に2ヶ所のヘテロ変異を認めた先天性脊椎骨端異形成症の1例
田島 敏広, 河野 修, 森川 俊太郎, 石津 桂, 日本内分泌学会雑誌, 91, 1, 370, 370, Apr. 2015
(一社)日本内分泌学会, Japanese

マススクリーニングの歴史と展望 内分泌疾患の新しい知見　　　　　　　　　　　　　　　
田島 敏広, 森川 俊太郎, 石津 桂, 中村 明枝, 日本小児科学会雑誌, 119, 2, 195, 195, Feb. 2015
(公社)日本小児科学会, Japanese

当院におけるビタミンD欠乏性くる病・ビタミンD欠乏症38例の検討　　　　　　　　　　　　　　　
石津 桂, 森川 俊太郎, 奥原 宏治, 田島 敏広, 日本小児科学会雑誌, 119, 2, 256, 256, Feb. 2015
(公社)日本小児科学会, Japanese

IGSF1異常による中枢性甲状腺機能低下症の2例
田島 敏広, 森川 俊太郎, 石津 桂, 藤倉 かおり, 日本マス・スクリーニング学会誌, 24, 2, 187, 187, Jul. 2014
(一社)日本マススクリーニング学会, Japanese

液体クロマトグラフ-タンデム質量分析計(LC-MS/MS法)によるステロイド分析が早期発見に有用であった21-水酸化酵素欠損症の1例
田島 敏広, 藤倉 かおり, 花井 潤師, 森川 俊太郎, 石津 桂, 山岸 卓弥, 田上 泰子, 宮田 淳, 福士 勝, 日本マス・スクリーニング学会誌, 24, 1, 39, 42, Jun. 2014
(一社)日本マススクリーニング学会, Japanese

ミューラー管抑制ホルモン遺伝子に新規変異が見つかったミューラー管遺残症の1例
中村 美智子, 守屋 仁彦, 森川 俊太郎, 三井 貴彦, 橘田 岳也, 石津 桂, 田島 敏広, 篠原 信雄, 日本小児泌尿器科学会雑誌, 23, 2, 169, 169, Jun. 2014
日本小児泌尿器科学会, Japanese

LC-MS/MS法によるステロイド分析が有用であった21-水酸化酵素欠損症の1例
田島 敏広, 藤倉 かおり, 石津 桂, 森川 俊太郎, 山岸 卓弥, 田上 泰子, 福士 勝, 宮田 淳, 日本内分泌学会雑誌, 90, 1, 330, 330, Apr. 2014
(一社)日本内分泌学会, Japanese

先天性下垂体形成不全の4例
田島 敏広, 森川 俊太郎, 中村 明枝, 石津 桂, 日本内分泌学会雑誌, 90, 1, 338, 338, Apr. 2014
(一社)日本内分泌学会, Japanese

膵管を通じて閉鎖部の前後への交通が認められた離断型十二指腸閉鎖の1例
石川 桂子, 舩越 徹, 林 俊治, 喜納 政哉, 高田 譲二, 浜田 弘巳, 谷口 宏太, 森川 俊太郎, 小杉山 清隆, 上野 倫彦, 田原 泰夫, 日本小児外科学会雑誌, 50, 1, 161, 161, Feb. 2014
(一社)日本小児外科学会, Japanese

栄養摂取不良の母体から出生し早発型ビタミンK欠乏による頭蓋内出血を来した双胎の1児例
森川 俊太郎, 恩田 哲雄, 早坂 格, 小杉山 清隆, 長 和俊, 日本未熟児新生児学会雑誌, 26, 1, 117, 123, Feb. 2014
(公社)日本新生児成育医学会, Japanese

マイコプラズマ肺炎の経過中、ミノサイクリンとアシクロビルに薬剤リンパ球刺激試験(DLST)強陽性を示したStevens-Johnson症候群の1例
森川 俊太郎, 上田 泰弘, 森岡 圭太, 小杉山 清隆, 兼古 理恵, 澤田 光男, 稲川 昭, 小児科臨床, 67, 1, 75, 79, Jan. 2014
(株)日本小児医事出版社, Japanese

新生児マス・スクリーニング検査でみつかったTPO異常症の2例
石津 桂, 森川 俊太郎, 鳴海 覚志, 長谷川 奉延, 田島 敏広, 日本内分泌学会雑誌, 89, 3, 977, 977, Dec. 2013
(一社)日本内分泌学会, Japanese

【小児内分泌学の進歩2014】甲状腺 Immunoglobulin superfamily member 1(IGSF1)遺伝子異常による先天性中枢性甲状腺機能低下症　　　　　　　　　　　　　　　
森川 俊太郎, 中村 明枝, 依藤 亨, 母坪 智行, 石津 桂, 田島 敏広, ホルモンと臨床, 61, 12, 945, 948, Dec. 2013
(有)医学の世界社, Japanese

【小児内分泌学の進歩2014】甲状腺 腹痛、低身長を契機として診断に至ったIGSF1遺伝子異常症の14歳男児例　　　　　　　　　　　　　　　
土山 厚志, 母坪 智行, 森川 俊太郎, 中村 明枝, 石津 桂, 田島 敏広, 森 俊彦, ホルモンと臨床, 61, 12, 949, 953, Dec. 2013
(有)医学の世界社, Japanese

腸重積を生じた回盲部非典型的Tリンパ球増殖症の一例 消化管原発末梢型T細胞リンパ腫?　　　　　　　　　　　　　　　
浜田 弘巳, 石川 桂子, 喜納 政哉, 森川 俊太郎, 小杉山 清隆, 藤岡 保範, 小林 良二, 日本小児血液・がん学会学術集会・日本小児がん看護学会・公益財団法人がんの子どもを守る会公開シンポジウムプログラム総会号, 55回・11回・18回, 321, 321, Nov. 2013
(NPO)日本小児血液・がん学会・(NPO)日本小児がん看護学会・(公財)がんの子供を守る会, Japanese

札幌市における30年間の先天性副腎皮質過形成症スクリーニング
石津 桂, 森川 俊太郎, 中村 明枝, 藤倉 かおり, 福士 勝, 母坪 智行, 花井 潤師, 宮田 淳, 田島 敏広, 日本内分泌学会雑誌, 89, 2, 624, 624, Sep. 2013
(一社)日本内分泌学会, Japanese

LC-MS/MS法によるステロイド分析が発見に有用であった21-水酸化酵素欠損症の1例
田島 敏広, 石津 桂, 中村 明枝, 森川 俊太郎, 藤倉 かおり, 山岸 卓弥, 田上 泰子, 花井 潤師, 宮田 淳, 福士 勝, 日本マス・スクリーニング学会誌, 23, 2, 225, 225, Aug. 2013
(一社)日本マススクリーニング学会, Japanese

腸重積を生じた回盲部非典型的Tリンパ球増殖症の1例
石川 桂子, 舩越 徹, 林 俊治, 喜納 政哉, 高田 譲二, 浜田 弘巳, 森川 俊太郎, 小杉山 清隆, 藤岡 保範, 日本小児外科学会雑誌, 49, 4, 959, 959, Jun. 2013
(一社)日本小児外科学会, Japanese

1歳5ヵ月時に十二指腸潰瘍の粘膜下異所性膵と潰瘍出血で発症し、潰瘍頻回再発を繰り返し、ランソプラゾールとメサラジンにより寛解を得た一例
小杉山 清隆, 早坂 格, 森川 俊太郎, 恩田 哲雄, 横山 和典, 浜田 弘巳, 日本小児栄養消化器肝臓学会雑誌, 27, 1, 49, 49, Apr. 2013
(一社)日本小児栄養消化器肝臓学会, Japanese

脳外科手術で発作消失した、内側型側頭葉てんかんの3例　　　　　　　　　　　　　　　
恩田 哲雄, 森川 俊太郎, 早坂 格, 小杉山 清隆, 白石 秀明, 溝渕 雅広, 鷲見 佳泰, 馬場 好一, 日本小児科学会雑誌, 116, 12, 1942, 1943, Dec. 2012
(公社)日本小児科学会, Japanese

川崎病の治療中に2度の発熱と皮疹を呈したGianotti症候群の1例
森川 俊太郎, 恩田 哲雄, 早坂 格, 小杉山 清隆, 兼古 理恵, 臨床小児医学, 60, 1-6, 47, 47, Dec. 2012
(財)小児愛育協会, Japanese

サイトメガロウイルス感染症を契機とし保存的治療で軽快した蛋白漏出性胃腸症の1例　　　　　　　　　　　　　　　
上田 泰弘, 森川 俊太郎, 森岡 圭太, 小杉山 清隆, 日本小児科学会雑誌, 116, 5, 883, 883, May 2012
(公社)日本小児科学会, Japanese

マイコプラズマ肺炎の経過中にミノマイシン(MINO)とアシクロビル(ACV)に薬剤リンパ球刺激試験(DLST)強陽性を示したStevens-Johnson症候群(SJS)の1例　　　　　　　　　　　　　　　
森川 俊太郎, 上田 泰弘, 森岡 圭太, 小杉山 清隆, 兼古 理恵, 澤田 光男, 稲川 昭, 日本小児科学会雑誌, 116, 5, 939, 939, May 2012
(公社)日本小児科学会, Japanese

脳室周囲白質軟化症(Periventricular leukomalacia:PVL)を認めた先天性筋強直性ジストロフィーの早産児例　　　　　　　　　　　　　　　
森岡 圭太, 上田 泰弘, 森川 俊太郎, 小杉山 清隆, 山崎 健史, 植木 将弘, 日本小児科学会雑誌, 115, 11, 1814, 1814, Nov. 2011
(公社)日本小児科学会, Japanese

筋炎を反復した小児シェーグレン症候群の1例
森川 俊太郎, 夘月 ゆたか, 服部 哲夫, 青柳 勇人, 小林 一郎, 臨床小児医学, 58, 1-6, 33, 33, Dec. 2010
(財)小児愛育協会, Japanese

B群溶連菌による化膿性膝関節炎の乳児例　　　　　　　　　　　　　　　
戸澤 雄介, 杉山 未奈子, 森川 俊太郎, 高橋 大介, 藤原 伸一, 野呂 歩, 鈴木 靖人, 仲西 正憲, 永島 哲郎, 興村 慎一郎, 木井 雄一郎, 堀 清成, 寺本 篤史, 井田 和功, 日本小児科学会雑誌, 114, 11, 1758, 1758, Nov. 2010
(公社)日本小児科学会, Japanese

当院妊婦の不規則抗体陽性者と児の黄疸、貧血の状況　　　　　　　　　　　　　　　
野呂 歩, 戸澤 雄介, 森川 俊太郎, 高橋 大介, 杉山 未奈子, 藤原 伸一, 鈴木 靖人, 仲西 正憲, 永島 哲郎, 日本小児科学会雑誌, 114, 10, 1611, 1611, Oct. 2010
(公社)日本小児科学会, Japanese

鉄剤治療への反応不良を契機として診断に至ったβサラセミアの1例　　　　　　　　　　　　　　　
高橋 大介, 森川 俊太郎, 戸澤 雄介, 杉山 未奈子, 藤原 伸一, 野呂 歩, 鈴木 靖人, 仲西 正憲, 永島 哲郎, 林 孝一, 小林 良二, 山城 安啓, 服部 幸夫, 日本小児科学会雑誌, 114, 9, 1461, 1462, Sep. 2010
(公社)日本小児科学会, Japanese

当院で経験した溶血性尿毒症症候群(HUS)2例の臨床的検討　　　　　　　　　　　　　　　
山崎 健史, 森岡 圭太, 高橋 俊行, 森川 俊太郎, 濱野 貴通, 佐野 仁美, 須藤 章, 福島 直樹, 日本小児科学会雑誌, 114, 8, 1232, 1232, Aug. 2010
(公社)日本小児科学会, Japanese

2歳児で発見された遅発型先天性横隔ヘルニアの1例　　　　　　　　　　　　　　　
森川 俊太郎, 高橋 俊行, 濱野 貴通, 山崎 健史, 佐野 仁美, 須藤 章, 福島 直樹, 大川 由美, 和田 雅孝, 田中 明彦, 三品 泰二郎, 日本小児科学会雑誌, 114, 8, 1234, 1234, Aug. 2010
(公社)日本小児科学会, Japanese

Cladribine使用後早期に2次性MDSを発症したランゲルハンス細胞組織球症症例
鈴木 大介, 安田 一恵, 小林 良二, 小林 邦彦, 杉山 未奈子, 森川 俊太郎, 戸澤 雄介, 高橋 大介, 藤原 伸一, 野呂 歩, 鈴木 靖人, 仲西 正憲, 永島 哲郎, 臨床小児医学, 57, 5-6, 116, 116, Dec. 2009
(財)小児愛育協会, Japanese

Cladribine使用後早期に2次性MDSを発症したランゲルハンス細胞組織球症症例　　　　　　　　　　　　　　　
鈴木 大介, 安田 一恵, 小林 良二, 杉山 美奈子, 森川 俊太郎, 戸澤 雄介, 高橋 大介, 藤原 伸一, 野呂 歩, 鈴木 靖人, 仲西 正憲, 永島 哲郎, 小児がん, 46, プログラム・総会号, 413, 413, Nov. 2009
(NPO)日本小児がん学会, Japanese

潰瘍性大腸炎を合併した原発性硬化性胆管炎の7歳男児例　　　　　　　　　　　　　　　
藤原 伸一, 寺下 友佳代, 高橋 大介, 戸澤 雄介, 森川 俊太郎, 杉山 未奈子, 野呂 歩, 鈴木 靖人, 仲西 正憲, 永島 哲郎, 窪田 満, 日本小児栄養消化器肝臓学会雑誌, 23, Suppl., 55, 55, Sep. 2009
(一社)日本小児栄養消化器肝臓学会, Japanese

アメーバ性肝膿瘍の1症例　　　　　　　　　　　　　　　
森川 俊太郎, 永坂 敦, 和田 英樹, 大西 礼造, 遠藤 文菜, 中村 路夫, 早川 敏文, 佐野 公昭, 西川 秀司, 樋口 晶文, 市立札幌病院医誌, 67, 2, 269, 271, Mar. 2008
市立札幌病院, Japanese

EST後出血に対し膵管ステント留置後APC止血を施行した1例　　　　　　　　　　　　　　　
和田 英樹, 中村 路夫, 森川 俊太郎, 大西 礼造, 檀浦 裕, 遠藤 文菜, 早川 敏文, 永坂 敦, 佐野 公昭, 西川 秀司, 樋口 晶文, 市立札幌病院医誌, 67, 2, 273, 274, Mar. 2008
市立札幌病院, Japanese