PMID: 15387959Sep 25, 2004Paper

Etiological dissection in common anti-islet autoantibody-negative patients with type 1 diabetes

Zhonghua yi xue za zhi
Dongmei ZhangLin Yang

Abstract

To explore the immunological and genetic factors of common anti-islet autoantibody-negative patients with type 1 diabetes. Specimens of peripheral blood were collected from 33 common autoantibody (GAD-Ab, IA2-Ab, IAA, TGA and TPO-Ab) negative diabetic patients with new-onset of unprovoked ketosis (or ketoacidosis), and genome DNA was extracted. The antibodies to carboxypeptide-H (CPH) and SOX13 (ICA12) were detected by radioligand assay. The gene mutations of MODY3 (HNF-1alpha) and MODY6 (NeuroD1/Beta2) were detected by PCR-SSCP sequencing. Mitochondrial gene mutations were analyzed with PCR-RFLP. Two (6%) of the patients were SOX13-Ab positive, while none of them was positive for CPH-Ab. Gene mutation detection found one case of a new mutation, R321H (CGC-->CAC) in the exon 5 of HNF-1alpha gene and one case with ND1 mt3316 G-->A mutation in mitochondrial DNA. In addition to the diabetes-associated mutations described above, seven polymorphisms of HNF-1alpha gene, including L17L, I27L, L459L, S487N, IVS5 + 9 C > G, IVS6-42 G > T, and IVS7 + 7 G > A, and one NeuroD1/Beta2 gene polymorphic variant Ala45Thr, were found. Autoimmunity and gene mutations (such as MODY3 and mitochondrial genes mutations) may be etiological in a few ca...Continue Reading

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