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% 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. 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 found NEUROG3 as a new causative gene for MODY.

Zhang, YananThird Affiliated Hospital of Sun Yat‐sen University (author)
Li, MaixinyueNanning Children’s Hospital (author)
Yan, JinhuaThird Affiliated Hospital of Sun Yat‐sen University (author)
Yang, DaizhiThird Affiliated Hospital of Sun Yat‐sen University (author)
Luo, SihuiUniversity of Science and Technology of China (author)
Zheng, XueyingUniversity of Science and Technology of China (author)
Yang, GuoqingGeneral Hospital of People's Liberation Army (author)
Li, ZhuoThird Affiliated Hospital of Sun Yat‐sen University (author)
Xu, WenThird Affiliated Hospital of Sun Yat‐sen University (author)
Groop, LeifLund University,Lunds universitet,Translationell muskelforskning,Forskargrupper vid Lunds universitet,Translational Muscle Research,Lund University Research Groups(Swepub:lu)endo-lgr (author)
Weng, JianpingThird Affiliated Hospital of Sun Yat‐sen University (author)
Third Affiliated Hospital of Sun Yat‐sen UniversityNanning Children’s Hospital (creator_code:org_t)

By the author/editor: Liang, Hua; Zhang, Yanan; Li, Maixinyue; Yan, Jinhua; Yang, Daizhi; Luo, Sihui; show more...; Zheng, Xueying; Yang, Guoqing; Li, Zhuo; Xu, Wen; Groop, Leif; Weng, Jianping; show less...

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MEDICAL AND HEALTH SCIENCES: MEDICAL AND HEAL ...; and Clinical Medicin ...; and Endocrinology an ...

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