小岛
医学
1型糖尿病
抗体
糖尿病
桑格测序
内科学
复合杂合度
内分泌学
免疫学
遗传学
突变
生物
基因
作者
Jayaram Menon,Pratibha Singh,Archana Archana,Preeti Singh,Medha Mittal,Uma Kanga,Kausik Mandal,Anju Seth,Vijayalakshmi Bhatia,Preeti Dabadghao,Siddhnath Sudhanshu,Atul Garg,Ruchira Vishwakarma,A. Sarangi,Shraddha Verma,Surya Kumar Singh,Eesh Bhatia
标识
DOI:10.1210/clinem/dgad644
摘要
While the frequency of islet antibody-negative (idiopathic) type 1 diabetes mellitus (T1DM) is reported to be increased in Indian children, its aetiology is not studied. We investigated the role of monogenic diabetes in the causation of islet antibody-negative T1DM.We conducted a multicentre, prospective, observational study of 169 Indian children (age 1-18 years) with recent-onset T1DM. All were tested for antibodies against GAD65, islet antigen-2 and zinc transporter 8, using validated ELISA. Thirty-four islet antibody-negative children underwent targeted next-generation sequencing for 31 genes implicated in monogenic diabetes using the Illumina platform. All mutations were confirmed by Sanger sequencing.Thirty-five (21%) children were negative for all islet antibodies. Twelve patients (7% of entire cohort, 34% of patients with islet antibody-negative T1DM) were detected to have pathogenic or likely pathogenic genetic variants. The most frequently affected locus was WFS1, with 9 patients (5% of entire cohort, 26% of islet antibody-negative). These included 7 children with homozygous, and 1 patient each with a compound heterozygous and heterozygous mutation. Children with Wolfram syndrome 1 (WS) presented with severe insulin-requiring diabetes (including 3 patients with ketoacidosis), but other syndromic manifestations were not detected. In 3 patients, heterozygous mutations in HNF4A, ABCC8 and PTF1A loci were detected.Nearly one-quarter of Indian children with islet antibody-negative T1DM had recessive mutations in the WFS1 gene. These patients did not exhibit other features of WS at the time of diagnosis. Testing for monogenic diabetes, especially WS, should be considered in Indian children with antibody-negative T1DM.
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