| Affiliation: | 1. Department of Endocrinology and Metabolism, The Third Affiliated Hospital of Sun Yat-sen University, Guangdong Provincial Key Laboratory of Diabetology, Guangzhou, China Hua Liang and Yanan Zhang contributed equally as the first author.;2. Department of Infertility and Sexual Medicine, The Third Affiliated Hospital of Sun Yat-Sen University, Guangzhou, China;3. Department of Clinical Laboratory, Nanning Children’s Hospital, Nanning, China;4. Department of Endocrinology and Metabolism, The Third Affiliated Hospital of Sun Yat-sen University, Guangdong Provincial Key Laboratory of Diabetology, Guangzhou, China;5. Division of Life Sciences and Medicine, Department of Endocrinology, The First Affiliated Hospital, University of Science and Technology of China, Hefei, China;6. Department of Endocrinology, Chinese PLA General Hospital, Beijing, China;7. Department of Clinical Sciences, Lund University Diabetes Center, Lund University, Malmö, Sweden |
| Abstract: | Aims/IntroductionGiven 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 MethodsMaturity‐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.ResultsA 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% for GCK, 15.79% for HNF1A, 2.63% for HNF4A, and 1.32% for KLF11, PAX4 and NEUROG3. 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 of NEUROG3 p.Arg55Glufs*23 is characterized by hyperglycemia and mild intermittent abdominal pain.ConclusionsThis 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 found NEUROG3 as a new causative gene for MODY. |
