論文

査読有り 国際誌
2018年3月

Comprehensive screening for monogenic diabetes in 89 Japanese children with insulin-requiring antibody-negative type 1 diabetes.

Pediatric diabetes
  • Kikumi Ushijima
  • Maki Fukami
  • Tadayuki Ayabe
  • Satoshi Narumi
  • Misako Okuno
  • Akie Nakamura
  • Toshikazu Takahashi
  • Kenji Ihara
  • Kazuhiro Ohkubo
  • Emiko Tachikawa
  • Shoji Nakayama
  • Junichi Arai
  • Nobuyuki Kikuchi
  • Toru Kikuchi
  • Tomoyuki Kawamura
  • Tatsuhiko Urakami
  • Kenichiro Hata
  • Kazuhiko Nakabayashi
  • Yoichi Matsubara
  • Shin Amemiya
  • Tsutomu Ogata
  • Ichiro Yokota
  • Shigetaka Sugihara
  • 全て表示

19
2
開始ページ
243
終了ページ
250
記述言語
英語
掲載種別
研究論文(学術雑誌)
DOI
10.1111/pedi.12544

BACKGROUND: Mutations in causative genes for neonatal diabetes or maturity-onset diabetes of the young have been identified in multiple patients with autoantibody-negative type 1 diabetes (T1D). OBJECTIVES: We aimed to clarify the prevalence and phenotypic characteristics of monogenic abnormalities among 89 children with autoantibody-negative insulin-requiring T1D. METHODS: Mutations in 30 genes were screened using next-generation sequencing, and copy-number alterations of 4 major causative genes were examined using multiplex-ligation-dependent probe amplification. We compared the clinical characteristics between mutation carriers and non-carriers. RESULTS: We identified 11 probable pathogenic substitutions (6 in INS , 2 in HNF1A , 2 in HNF4A , and 1 in HNF1B ) in 11 cases, but no copy-number abnormalities. Only 2 mutation carriers had affected parents. De novo occurrence was confirmed for 3 mutations. The non-carrier group, but not the carrier group, was enriched with susceptible HLA alleles. Mutation carriers exhibited comparable phenotypes to those of non-carriers, except for a relatively normal body mass index (BMI) at diagnosis. CONCLUSIONS: This study demonstrated significant genetic overlap between autoantibody-negative T1D and monogenic diabetes. Mutations in INS and HNF genes, but not those in GCK and other monogenic diabetes genes, likely play critical roles in children with insulin-requiring T1D. This study also suggests the relatively high de novo rates of INS and HNF mutations, and the etiological link between autoimmune abnormalities and T1D in the non-carrier group. Carriers of monogenic mutations show non-specific phenotypes among all T1D cases, although they are more likely to have a normal BMI at diagnosis than non-carriers.

リンク情報
DOI
https://doi.org/10.1111/pedi.12544
PubMed
https://www.ncbi.nlm.nih.gov/pubmed/28597946
Web of Science
https://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcAuth=JSTA_CEL&SrcApp=J_Gate_JST&DestLinkType=FullRecord&KeyUT=WOS:000425109500009&DestApp=WOS_CPL
ID情報
  • DOI : 10.1111/pedi.12544
  • ISSN : 1399-543X
  • PubMed ID : 28597946
  • Web of Science ID : WOS:000425109500009

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