Recognition of maturity-onset diabetes of the young in China

Aims/Introduction Given that mutations related to maturity-onset diabetes of the young (MODY) are rarely found in Chinese populations, we aim to characterize the mutation spectrum of MODY pedigrees. Materials and Methods Maturity-onset diabetes of the young candidate gene- or exome-targeted capture sequencing was carried out in 76 probands from unrelated families fulfilling the clinical diagnostic criteria for MODY. MAF <0.01 in the GnomAD or ExAC database was used to filter significant variants. Sanger sequencing was then carried out to validate findings. Function prediction by SIFT, PolyPhen-2 and PROVEAN or CADD was carried out in missense mutations. Results A total of 32 mutations in six genes were identified in 31 families, accounting for 40.79% of the potential MODY families. The MODY subtype detection rate was 18.42% forGCK, 15.79% forHNF1A, 2.63% forHNF4A, and 1.32% forKLF11,PAX4andNEUROG3. Seven nonsense/frameshift mutations and four missense mutations with damaging prediction were newly identified novel mutations. The clinical features of MODY2, MODY3/1 and MODYX are similar to previous reports. Clinical phenotype ofNEUROG3p.Arg55Glufs*23 is characterized by hyperglycemia and mild intermittent abdominal pain. Conclusions This study adds to the emerging pattern of MODY epidemiology that the proportion of MODY explained by known pathogenic genes is higher than that previously reported, and foundNEUROG3as a new causative gene for MODY.