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Recognition of maturity-onset diabetes of the young in China

Liang, Hua ; Zhang, Yanan ; Li, Maixinyue ; Yan, Jinhua ; Yang, Daizhi ; Luo, Sihui ; Zheng, Xueying ; Yang, Guoqing ; Li, Zhuo and Xu, Wen , et al. (2021) In Journal of Diabetes Investigation 12(4). p.501-509
Abstract

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,... (More)

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.

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organization
publishing date
type
Contribution to journal
publication status
published
subject
keywords
Chinese, Maturity-onset diabetes of the young, Pathogenic genes
in
Journal of Diabetes Investigation
volume
12
issue
4
pages
501 - 509
publisher
Wiley-Blackwell
external identifiers
  • pmid:32741144
  • scopus:85090472957
ISSN
2040-1116
DOI
10.1111/jdi.13378
language
English
LU publication?
yes
id
6a0a638a-5e30-4ff9-ba97-13f6e8cfe784
date added to LUP
2020-10-02 12:55:45
date last changed
2021-06-08 04:11:20
@article{6a0a638a-5e30-4ff9-ba97-13f6e8cfe784,
  abstract     = {<p>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 &lt;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.</p>},
  author       = {Liang, Hua and Zhang, Yanan and Li, Maixinyue and Yan, Jinhua and Yang, Daizhi and Luo, Sihui and Zheng, Xueying and Yang, Guoqing and Li, Zhuo and Xu, Wen and Groop, Leif and Weng, Jianping},
  issn         = {2040-1116},
  language     = {eng},
  number       = {4},
  pages        = {501--509},
  publisher    = {Wiley-Blackwell},
  series       = {Journal of Diabetes Investigation},
  title        = {Recognition of maturity-onset diabetes of the young in China},
  url          = {http://dx.doi.org/10.1111/jdi.13378},
  doi          = {10.1111/jdi.13378},
  volume       = {12},
  year         = {2021},
}