Islet autoimmunity and genetic mutations in Chinese subjects initially thought to have Type 1B diabetes

Aims  To explore the contribution of islet autoimmunity and genetic mutations in Chinese patients initially thought to have Type 1B diabetes. Methods  A group of 33 Chinese patients with newly diagnosed Type 1B diabetes, were identified by the absence of autoantibodies to glutamic acid decarboxylase (GAD), IA‐2, insulin, thyroid globulin or thyroid peroxidase, or high‐risk HLA‐DQ haplotypes. The cohort was further characterized by measurement of autoantibodies to carboxypeptidase H (CPH) and SOX13 using radioligand assays, and testing for genetic mutations associated with MODY3/MODY6 and mitochondrial diabetes. Mutations of HNF‐1α (MODY3) and neuroD1/β2 (MODY6) genes were screened using the single‐strand conformation polymorphism (SSCP) technique and sequencing. Mitochondrial DNA mutations were analysed with polymerase chain reaction—restriction fragment length polymorphism (PCR‐RFLP). Results  Within the cohort, we found one patient with a novel mutation, R321H (CGC→CAC) in exon 5 of the HNF‐1α gene, one with ND1 mt3316 G→A mutation in mitochondrial DNA, five with Ala45Thr polymorphisms in the neuroD1/β2 gene, and two patients with autoantibodies to SOX13. Conclusions  Some of the Chinese patients originally thought to have Type 1B diabetes do have other evidence of islet autoimmunity and genetic mutations involved in the underlying aetiology. This suggests that more rigorous screening for these conditions is needed before classifying subjects as having Type 1B diabetes.