Islet autoimmunity and genetic mutations in Chinese subjects initially thought to have Type 1B diabetes.
OBJECTIVE
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-1alpha (MODY3) and neuroD1/beta2 (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-1alpha gene, one with ND1 mt3316 G-->A mutation in mitochondrial DNA, five with Ala45Thr polymorphisms in the neuroD1/beta2 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.
Zhang
D
D
Diabetes Center, Institute of Metabolism and Endocrinology, The Second Xiangya Hospital, Central South University, Changsha, Hunan, China.
Zhou
Z
Z
Li
L
L
Weng
J
J
Huang
G
G
Jing
P
P
Zhang
C
C
Peng
J
J
Xiu
L
L
D000293:Adolescent; D000328:Adult; D000368:Aged; D001323:Autoantibodies / Q000032:analysis; D001324:Autoantigens / Q000276:immunology; D015551:Autoimmunity / Q000235:genetics / Q000276:immunology*; D051792:Basic Helix-Loop-Helix Proteins / Q000235:genetics; D043423:Carboxypeptidase H / Q000276:immunology; D015331:Cohort Studies; D004272:DNA, Mitochondrial / Q000032:analysis; D003922:Diabetes Mellitus, Type 1 / Q000235:genetics* / Q000276:immunology; D005192:Family Health; D005260:Female; D005951:Glucose Tolerance Test; D051538:Hepatocyte Nuclear Factor 1-alpha / Q000235:genetics; D006609:High Mobility Group Proteins / Q000276:immunology; D006801:Humans; D007515:Islets of Langerhans / Q000276:immunology*; D008297:Male; D008875:Middle Aged; D010375:Pedigree; D011110:Polymorphism, Genetic / Q000235:genetics; D055755:SOXD Transcription Factors
D001323:Autoantibodies; D001324:Autoantigens; D051792:Basic Helix-Loop-Helix Proteins; D043423:Carboxypeptidase H; D004272:DNA, Mitochondrial; D051538:Hepatocyte Nuclear Factor 1-alpha; D006609:High Mobility Group Proteins; D055755:SOXD Transcription Factors; C093970:NEUROD1 protein, human; C491720:SOX13 protein, human