2018 Fiscal Year Final Research Report
Growth hormone insensitivity due to anomalies of insulin-like growth factor systems
| Project/Area Number |
16K09989
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Multi-year Fund |
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| Section | 一般 |
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| Research Field |
Pediatrics
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| Research Institution | Tottori University |
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Principal Investigator |
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| Co-Investigator(Kenkyū-buntansha) |
岡田 晋一 鳥取大学, 医学部, 准教授 (50343281)
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| Research Collaborator |
KAWASHIMA yuki
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| Project Period (FY) |
2016-04-01 – 2019-03-31
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| Keywords | IGF不応症 / SGA性低身長症 / インスリン様成長因子 / IGF受容体異常症 / インスリン受容体基質１ / IRS1 / acid labile substance / ALS |
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| Outline of Final Research Achievements |
Proband is a 14-year-old Japanese girl with SGA short stature. Her GH treatment did not improve her height. Additionally there was family history of SGA short stature. We decided to analyzed GH/IGF related genes in this family
Heterozygous missense mutation of acid labile subunit (ALS) gene (p.Arg229His) was detected in proband and her father with normal stature. Heterogeneous deletion of IRS1 gene (p.Ser685_Ser686del) was observed in proband, her elder sister and mother who were SGA short stature. We evaluated the function of these two mutated gene. ALS production in mutated IGFALS transfected cells was lower than that of wild type. Mutated IRS1 gene transfected cells decrease the IRS1 expression and phosphorylation of AKT is suppressed compared with wild type. Her father bearing same ALS mutation has normal stature whereas her sister and mother bearing IRS1 mutation show SGA short stature. Therefore, we believe IRS1 mutation is the cause of short stature of this family.
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| Free Research Field |
小児内分泌学
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| Academic Significance and Societal Importance of the Research Achievements |
体内発育遅延（SGA）性低身長症に対するGH治療が開始されたが、GH治療の効果が乏しい症例も存在する。SGAの原因の大半は胎内での栄養不良状態に起因しているが、IGF KOマウスがSGAを示したことから、IGF系の異常もSGA性低身長の原因となることが明らかになっている。
私たちはIGF受容体異常症でSGA性低身長となった症例を報告してきたが、今回はGH治療が不応であったSGA性低身長症の女児にIGF受容体の下流に存在するIRS1に変異を見出し、それがSGA性低身長の原因となっていることを明らかにした。
IRS1異常はGH治療に抵抗するSGA性低身長症の新しい病因である。
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