Molecular and phenotypic characteristics of maturity‐onset diabetes of the young compared with early onset type 2 diabetes in <scp>C</scp>hina

Zhang, Manna; Zhou, Jiao Jiao; Cui, Wei; Li, Yan; Yang, Peng; Chen, Xiaoyun; Sheng, Chunjun; Li, Hong; Qu, Shen

doi:10.1111/1753-0407.12253

Cited by 13 publications

(14 citation statements)

References 24 publications

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“…In the present study, 24/42 (57%) clinically suspected MODY cases had mutations identified. In contrast, a study from China suggested that MODY‐X (mutation of MODY genes was absent) accounted for the majority of clinical MODY cases in China . Our results are markedly different from previous findings in adult Chinese patients.…”

Section: Discussioncontrasting

confidence: 99%

Molecular diagnosis of maturity‐onset diabetes of the young in a cohort of Chinese children

Lin

Sheng

et al. 2020

Pediatr Diabetes

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Objective: The purpose of this study was to investigate the molecular basis of maturity-onset diabetes of the young (MODY) by whole-exome sequencing (WES) and estimate the frequency and describe the clinical characteristics of MODY in southern China. Methods: Genetic analysis was performed in 42 patients with MODY aged 1 month to 18 years among a cohort of 759 patients with diabetes, identified with the following four clinical criteria: age of diagnosis ≤18 years; negative pancreatic autoantibodies; family history of diabetes; or persistently detectable C-peptide; or diabetes associated with extrapancreatic features. GCK gene mutations were first screened by Sanger sequencing. GCK mutation-negative patients were further analyzed by WES. Results: Mutations were identified in 24 patients: 20 mutations in GCK, 1 in HNF4A, 1 in INS, 1 in ABCC8, and a 17q12 microdeletion. Four previously unpublished novel GCK mutations: c.1108G>C in exon 9, and c.1339C>T, c.1288_1290delCTG, and c.1340_1343delGGGGinsCTGGTCT in exon 10 were detected. WES identified a novel missense mutation c.311A>G in exon 3 in the INS gene, and copy number variation analysis detected a 1.4 Mb microdeletion in the long arm of the chromosome 17q12 region. Compared with mutation-negative subjects, the mutation-positive subjects had lower hemoglobin A1c and initial blood glucose levels. Conclusions: Most MODY cases in this study were due to GCK mutations, which is in contrast to previous reports in Chinese patients. Diabetes associated with extrapancreatic features should be a clinical criterion for MODY genetic analysis. Mutational analysis by WES provided a precise diagnosis of MODY subtypes. Moreover, WES can be useful for detecting large deletions in coding regions in addition to point mutations. K E Y W O R D S childhood, maturity-onset diabetes of the young, South China, whole-exome sequencing Aijing Xu and Yunting Lin contribute equally to this work.

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Section: Discussioncontrasting

confidence: 99%

Molecular diagnosis of maturity‐onset diabetes of the young in a cohort of Chinese children

Lin

Sheng

et al. 2020

Pediatr Diabetes

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“…Families with MODY2 account for 1% of 146 unrelated Chinese families with MODY [5]. Zhang et al studied 14 Chinese families with MODY and did not find any GCK mutation or the other 12 known MODY genes [6]. Patients with MODY2 are usually asymptomatic, and diabetes is not always present in their family history.…”

Section: Discussionmentioning

confidence: 99%

“…Furthermore, MODY2 accounts for only 1% of Chinese MODY patients [5]. Recently, Zhang et al studied 14 Chinese MODY probands from unrelated families and 59 patients (age at onset ≤ 35 years) diagnosed as early onset T2DM, as well as nucleotide variations in promoters, exons and exon-intron boundaries of 13 known MODY genes by sequencing, and they did not find any GCK mutation or the other 12 known MODY genes [6]. Interestingly, we found three Chinese families with MODY2 over a short period of time.…”

Section: Introductionmentioning

confidence: 99%

GCK mutations in Chinese MODY2 patients: a family pedigree report and review of Chinese literature

Xiao

Fang

et al. 2016

Journal of Pediatric Endocrinology and Metabolism

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“…Globally, MODY2 and MODY3 mutations constitute approximately 70% of MODY cases [ 12 ], while the other four types of MODY are more rarely found. For Asians, however, only 7.5%–10.3% of patients have mutations in MODY2 and MODY3 [ 13 ], and MODY with unknown cause (MODYX) accounts for 80–90% of clinical MODY cases [ 14 ].…”

Section: Introductionmentioning

confidence: 99%

“…There are, however, few reports concerning MODY gene mutations in Han Chinese families; thus additional mutational profiling is needed [ 13 , 14 ]. In this study, we screened 6 MODY genes ( HNF4A , GCK , HNF1A , IPF1 , HNF1B , and NEUROD1 ) for mutations in a Han Chinese family with suspected early-onset maternally inherited type 2 diabetes.…”

Section: Introductionmentioning

confidence: 99%

Identification of HNF4A Mutation p.T130I and HNF1A Mutations p.I27L and p.S487N in a Han Chinese Family with Early-Onset Maternally Inherited Type 2 Diabetes

Yang

Zhou

Liu

et al. 2016

Journal of Diabetes Research

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Maturity-onset diabetes of the young (MODY) is characterized by the onset of diabetes before the age of 25 years, positive family history, high genetic predisposition, monogenic mutations, and an autosomal dominant mode of inheritance. Here, we aimed to investigate the mutations and to characterize the phenotypes of a Han Chinese family with early-onset maternally inherited type 2 diabetes. Detailed clinical assessments and genetic screening for mutations in the HNF4α, GCK, HNF-1α, IPF-1, HNF1β, and NEUROD1 genes were carried out in this family. One HNF4A mutation (p.T130I) and two HNF1A polymorphisms (p.I27L and p.S487N) were identified. Mutation p.T130I was associated with both early-onset and late-onset diabetes and caused downregulated HNF4A expression, whereas HNF1A polymorphisms p.I27L and p.S487N were associated with the age of diagnosis of diabetes. We demonstrated that mutation p.T130I in HNF4A was pathogenic as were the predicted polymorphisms p.I27L and p.S487N in HNF1A by genetic and functional analysis. Our results show that mutations in HNF4A and HNF1A genes might account for this early-onset inherited type 2 diabetes.

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Molecular and phenotypic characteristics of maturity‐onset diabetes of the young compared with early onset type 2 diabetes in China

Abstract: Herein we report on 14 Chinese families with MODYX and describe its phenotype. Compared with early onset T2D, MODYX is characterized by lower BMI and decreased insulin-secreting capacity.

Cited by 13 publications

References 24 publications

Molecular diagnosis of maturity‐onset diabetes of the young in a cohort of Chinese children

Molecular diagnosis of maturity‐onset diabetes of the young in a cohort of Chinese children

GCK mutations in Chinese MODY2 patients: a family pedigree report and review of Chinese literature

Identification of HNF4A Mutation p.T130I and HNF1A Mutations p.I27L and p.S487N in a Han Chinese Family with Early-Onset Maternally Inherited Type 2 Diabetes

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