Scanning for MODY5 gene mutations in Chinese early onset or multiple affected diabetes pedigrees

Abstract

Mutation of HNF-1β gene has been reported in early onset diabetes or MODY families and this gene has been defined as MODY5 gene. The aim of our study was to examine whether HNF-1β mutation contribute to early onset or multiple affected diabetes pedigrees in Chinese. Molecular scanning of HNF-1β gene promoter region, nine exons and flanking introns was performed in 154 unrelated probands from early onset and multiple affected diabetes Chinese pedigrees. The family members of probands with mutations or variants and 58 nondiabetics were also examined. Clinical examinations of renal morphology, renal function and β-cell function were performed in the HNF-1β gene mutation carriers and family members. Mutation of HNF-1β gene causing the substitution S36F was found in two subjects of an early onset diabetic family. One carrier has early onset diabetes, renal function impairment and renal cyst, while the other has impaired glucose tolerance only. This is the first case of MODY5 gene mutation diabetes found in the Chinese. Three HNF-1β variants were identified and no significant differences in allele frequencies for these variants were detected between the nondiabetic and diabetic groups. Nucleotide 66 of intron 8 of HNF-1β gene was G in the Chinese population rather than A as noted in the GenBank sequence. These results suggest that HNF-1β gene mutations may be associated with nondiabetic renal dysfunction and diabetes in Chinese, but they are responsible for only a small percentage of early onset or multiple affected diabetes pedigrees including MODY.