KEIO RESEARCHERS INFORMATION SYSTEM

Profile 【 Display / hide 】

Profile 【 Display / hide 】

• 2001年慶大医学部卒業。母校の小児科学教室で4年間の臨床研修を行う。2005年から先天性内分泌疾患の分子遺伝学的研究に従事。2009年、慶應義塾大学大学院所定単位取得退学（同年、医学博士号取得）。博士研究員として研究を継続し、2012年には独力で次世代シーケンシング技術を用いた先天性内分泌疾患の包括的遺伝子診断システムを構築。MIRAGE症候群の発見 (Narumi S et al., Nat Genet 2016)などの成果を挙げた。2016年から2023年まで国立成育医療研究センター研究所で室長として活動。2023年から現職。
  
  日本小児科学会フェロー賞、日本内分泌学会研究奨励賞、日本甲状腺学会七條賞、日本小児内分泌学会学術賞、日本人類遺伝学会奨励賞、慶應医学賞ライジング・スター賞、日本小児科学会学術研究賞など受賞多数。

Career 【 Display / hide 】

Career 【 Display / hide 】

• 2001.05

  -

  2003.06

  Resident, Keio University Hospital (Department of Pediatrics)

• 2003.07

  -

  2005.06

  Physician, Department of Pediatrics, Kawasaki Municipal Hospital

• 2009.04

  -

  2016.03

  慶應義塾大学医学部　小児科学　特任助教

• 2016.04

  -

  2023.03

  国立成育医療研究センター, 分子内分泌研究部, 基礎内分泌研究室長

• 2023.04

  -

  Present

  慶應義塾大学医学部　小児科学　教授

Academic Background 【 Display / hide 】

Academic Background 【 Display / hide 】

• 2001.03

  Keio University, 医学部

  University, Graduated

• 2009.11

  Keio University, Medicine, Internal Medicine

  Graduate School, Withdrawal after completion of doctoral course requirements, Doctoral course

Academic Degrees 【 Display / hide 】

Academic Degrees 【 Display / hide 】

• Ph.D., Keio University, Coursework, 2009.11

Research Areas 【 Display / hide 】

Research Areas 【 Display / hide 】

• Life Science / Embryonic medicine and pediatrics

Research Keywords 【 Display / hide 】

Research Keywords 【 Display / hide 】

• Human genetics

• Endocrinology

• Pediatrics

• Thyroid

Research Themes 【 Display / hide 】

Research Themes 【 Display / hide 】

• Genomewide Copy Number Analysis in Patients with Thyroid Dysgenesis, 

  2009

  -

  2011

  　View Summary

  We tested whether copy number variations are involved in etiology of thyroid dysgenesis in this study.

Papers 【 Display / hide 】

Papers 【 Display / hide 】

• A thyroid adenoma in a pubertal male with thyroxine-binding globulin deficiency

  Kim H., Naiki Y., Iwahashi-Odano M., Narumi S., Ito K., Ishiguro A.

  Clinical Pediatric Endocrinology （Clinical Pediatric Endocrinology)  33 （ 1 ） 23 - 26 2024.01

  ISSN  09185739

  　View Summary

  Complete deficiency of thyroxin-binding globulin (TBG-CD) is not commonly associated with clinical symptoms, and little is known about thyroid tumors associated with TBG-CD. We present a case report of an asymptomatic follicular adenoma that spontaneously shrank in a patient with TBG-CD. A previously healthy 13-yr-old male presented with a diffusely swollen thyroid gland. Thyroid function tests revealed low total thyroxin and TBG concentrations, indicating a TBG deficiency. Ultrasonography revealed a mildly swollen thyroid gland with a nodule (14 × 12 × 19 mm) in the left lobe. Genetic analysis of peripheral blood revealed a previously reported SERPINA7 variant, which resulted in complete loss of TBG function. The nodule was identified as a follicular adenoma using fine-needle aspiration. Subsequently, the adenoma shrank without treatment. This pubertal case suggests that careful observation with ultrasonography is warranted for follicular adenoma in patients with TBG deficiency and that treatment may not be required.

  • Access to Document (DOI)

• A Small-for-Gestational-Age Infant with MIRAGE Syndrome Who Developed Heat Stroke and Rhabdomyolysis due to Severe Temperature Instability

  Saito K., Nakagawa R., Narumi S., Ohashi H., Ishiguro A., Kabe K.

  Neonatology （Neonatology)  120 （ 3 ） 390 - 394 2023.07

  ISSN  16617800

  　View Summary

  MIRAGE syndrome is characterized by myelodysplasia, infection, restriction of growth, adrenal hypoplasia, genital phenotypes, and enteropathy. This report describes heat stroke and rhabdomyolysis caused by anhidrosis as a symptom of MIRAGE syndrome in a small-for-gestational-age (SGA) female neonate born at 32 weeks of gestation (birth weight, 911 g [-3.8 SD]). She developed severe temperature instability with anhidrosis, growth failure, mild developmental delay, hypothyroidism, and intractable enteropathy. On day 156, her temperature reached 42.0°C; her fever persisted for 2 h with prolonged irritability. Her serum creatine kinase level increased to a peak value of 12,716 (normal range, 43-321) IU/L. The clinical feature was diagnosed as rhabdomyolysis caused by heat stroke, which resulted from physical exertion with anhidrosis. Her SAMD9 variant was c.2945G>A, p. (Arg982His). Neonatologists should be aware of MIRAGE syndrome as a differential diagnosis of SGA with temperature instability.

  • Access to Document (DOI)

• Differential toxicity and localization of arginine-rich C9ORF72 dipeptide repeat proteins depend on de-clustering of positive charges

  Miyagi T., Ueda K., Sugimoto M., Yagi T., Ito D., Yamazaki R., Narumi S., Hayamizu Y., Uji-i H., Kuroda M., Kanekura K.

  iScience （iScience)  26 （ 6 ）  2023.06

  　View Summary

  Arginine-rich dipeptide repeat proteins (R-DPRs), poly(PR) and poly(GR), translated from the hexanucleotide repeat expansion in the amyotrophic lateral sclerosis (ALS)-causative C9ORF72 gene, contribute significantly to pathogenesis of ALS. Although both R-DPRs share many similarities, there are critical differences in their subcellular localization, phase separation, and toxicity mechanisms. We analyzed localization, protein-protein interactions, and phase separation of R-DPR variants and found that sufficient segregation of arginine charges is necessary for nucleolar distribution. Proline not only efficiently separated the charges, but also allowed for weak, but highly multivalent binding. In contrast, because of its high flexibility, glycine cannot fully separate the charges, and poly(GR) behaves similarly to the contiguous arginines, being trapped in the cytoplasm. We conclude that the amino acid that spaces the arginine charges determines the strength and multivalency of the binding, leading to differences in localization and toxicity mechanisms.

  • Access to Document (DOI)

• Adult Thyroid Outcomes of Congenital Hypothyroidism

  Sugisawa C., Narumi S., Tanase-Nakao K., Hoshiyama A., Suzuki N., Ohye H., Fukushita M., Matsumoto M., Yoshihara A., Watanabe N., Sugino K., Hishinuma A., Noh J.Y., Katoh R., Taniyama M., Ito K.

  Thyroid （Thyroid)  33 （ 5 ） 556 - 565 2023.05

  ISSN  10507256

  　View Summary

  Background: More than 40 years have passed since the introduction of newborn screening (NBS) for congenital hypothyroidism (CH), and many early diagnosed patients have reached adulthood. Their thyroid morphology and function have been little studied. This cross-sectional, observational study was conducted to characterize the thyroid morphology and function of adult CH patients diagnosed in the framework of NBS for CH. Methods: A total of 103 adult CH patients born after 1979 were enrolled at Ito Hospital, Tokyo, Japan, and were classified into Goiter, Normal gland, and Dysgenesis groups based on ultrasonographic findings. For 60 patients, genetic analysis was performed. Thyroid function test results and the proportion of patients with thyroid nodules were compared among the three groups and between 56 female CH patients and 168 non-CH women matched for thyrotropin levels. Results: A significantly low serum free triiodothyronine/free thyroxine ratio (0.22) was observed in the Dysgenesis group. Thyroid nodules were detected in 14.3% (8/56) of female CH patients, more frequently than in non-CH women. Thyroid nodules were detected most frequently in the Goiter group (71%, 10/14). Genetic defects were identified in 89% (8/9) of patients belonging to the Goiter group, including thyroglobulin defect (33%, 3/9), thyroid peroxidase defect (33%, 3/9), and dual oxidase 2 defect (22%, 2/9). Conclusions: Our results suggest that adults with thyroid dysgenesis on levothyroxine replacement therapy have relative triiodothyronine deficiency. Most adults with goitrous CH have genetic dyshormonogenesis. They are at high risk of developing thyroid nodules. Our findings support the current guideline recommendation that CH patients with dyshormonogenesis should undergo periodic thyroid ultrasonography.

  • Access to Document (DOI)

• Cord Blood Transplantation in 2 Infants Presenting Monosomy 7 Clonal Hematopoiesis: SAMD9 / SAMD9L Germline Mutation

  Hirai M., Yagasaki H., Kanezawa K., Ueno M., Shimozawa K., Imai K., Morio T., Kato M., Gocho Y., Narumi S., Ebihara Y., Morioka I.

  Journal of Pediatric Hematology/Oncology （Journal of Pediatric Hematology/Oncology)  45 （ 2 ） E290 - E293 2023.03

  ISSN  10774114

  　View Summary

  Recently, germline mutations in SAMD9 and SAMD9L were increasingly found in children with monosomy 7. We report the outcomes in 2 infants with the SAMD9/SAMD9L variant, who presented with anemia and thrombocytopenia (patient 1), and neutropenia and nonsymptomatic white-matter-encephalopathy (patient 2). Both patients received cord blood transplantation and experienced critical post-cord blood transplantation adverse events; patients 1 and 2 developed fulminant engraftment syndrome and life-threatening graft-versus-host disease, respectively. Of note, selective loss of chromosome 7 in bone marrow-derived CD34+ cells was inferred.

  • Access to Document (DOI)

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Papers, etc., Registered in KOARA 【 Display / hide 】

Papers, etc., Registered in KOARA 【 Display / hide 】

• The pathogenesis of MIRAGE syndrome revealed by model mice using genome editing

  Narumi, Satoshi

  科学研究費補助金研究成果報告書 2020

• Model cell-line and model animals of MIRAGE syndrome

  Narumi, Satoshi

  科学研究費補助金研究成果報告書 2017

• Functional characterization of a novel TSH receptor mutation (V711fs) with protein instability

  Narumi, Satoshi

  科学研究費補助金研究成果報告書 2014

• Can simultaneous mutations in TSHR and DUOX2 cause congenital hypothyroidism?

  Narumi, Satoshi

  科学研究費補助金研究成果報告書 2013

• Prevalence, clinical manifestation, and molecular mechanism of congenital hypothyroidism due to DUOX2 abnormality

  Narumi, Satoshi

  科学研究費補助金研究成果報告書 2013

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Reviews, Commentaries, etc. 【 Display / hide 】

Reviews, Commentaries, etc. 【 Display / hide 】

• Parathyroid adenoma with a somatic CASR pathogenic variant: A pediatric case report

  Kawata K., Sato T., Honda M., Narumi S., Kameyama K., Ishii T., Hasegawa T.

  Pediatric Blood and Cancer (Pediatric Blood and Cancer)  70 ( 12 )  2023.12

  ISSN  15455009

  • Access to Document (DOI)

• A novel missense variant of FGFR1 in a Japanese girl with Kallmann syndrome and holoprosencephaly

  Uchida N., Mizuno Y., Seno S., Koyama Y., Takahashi T., Shibata H., Narumi S., Hasegawa T., Ishii T.

  Clinical Pediatric Endocrinology (Clinical Pediatric Endocrinology)  32 ( 1 ) 79 - 81 2023

  ISSN  09185739

  • Access to Document (DOI)

• Clinical and Immunological Analyses of Ten Patients with MIRAGE Syndrome

  Mitsui-Sekinaka K., Narumi S., Sekinaka Y., Uematsu K., Yoshida Y., Amano N., Shima H., Hasegawa T., Nonoyama S.

  Journal of Clinical Immunology (Journal of Clinical Immunology)  41 ( 3 ) 709 - 711 2021.04

  ISSN  02719142

  • Access to Document (DOI)

Research Projects of Competitive Funds, etc. 【 Display / hide 】

Research Projects of Competitive Funds, etc. 【 Display / hide 】

• 非コード領域に着目した先天性内分泌疾患に関わるゲノム異常の研究

  2023.04

  -

  2027.03

  基盤研究(B), Principal investigator

Awards 【 Display / hide 】

Awards 【 Display / hide 】

• 日本小児内分泌学会　最優秀演題賞

  2023, 日本小児内分泌学会

  Type of Award： Award from Japanese society, conference, symposium, etc.

• 日本小児科学会　学術研究賞

  2022, 日本小児科学会

  Type of Award： Award from Japanese society, conference, symposium, etc.

• 慶應医学賞　ライジング・スター賞

  2019, 慶應義塾

  Type of Award： Keio commendation etc.

• 日本小児内分泌学会　最優秀演題賞

  2019, 日本小児内分泌学会

  Type of Award： Award from Japanese society, conference, symposium, etc.

• 日本甲状腺学会　基礎医学研究助成

  2017, 日本甲状腺学会

  Type of Award： Award from Japanese society, conference, symposium, etc.

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Courses Taught 【 Display / hide 】

Courses Taught 【 Display / hide 】

• PEDIATRICS: SEMINAR

  2024

• PEDIATRICS: PRACTICE

  2024

• LECTURE SERIES, PEDIATRICS

  2024

• DEVELOPMENTAL MEDICINE

  2024

• CLINICAL CLERKSHIP IN PEDIATRICS

  2024

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Memberships in Academic Societies 【 Display / hide 】

Memberships in Academic Societies 【 Display / hide 】

• 日本甲状腺学会, 

  2009.04

  -

  Present

• 日本内分泌学会, 

  2005.04

  -

  Present

• 日本人類遺伝学会, 

  2005.04

  -

  Present

• 日本小児内分泌学会, 

  2004.04

  -

  Present

• 日本小児科学会, 

  2001.04

  -

  Present

Committee Experiences 【 Display / hide 】

Committee Experiences 【 Display / hide 】

• 2009.04

  -

  Present

  Member, 日本甲状腺学会

• 2005.04

  -

  Present

  会員, 日本内分泌学会

• 2005.04

  -

  Present

  会員, 日本人類遺伝学会

  　View Remarks

  2009年-　臨床遺伝専門医

• 2005.04

  -

  Present

  Member, 日本内分泌学会

• 2005.04

  -

  Present

  Member, 日本人類遺伝学会

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