Dataset Information

A Single Nucleotide Variant in HNF-1? is Associated with Maturity-Onset Diabetes of the Young in a Large Chinese Family.

ABSTRACT: Maturity-onset diabetes of the young (MODY) is a heterogeneous entity of monogenic disorders characterized by autosomal dominant inheritance. Eleven genes were related, including HNF4?, GCK, HNF1?, IPF1, and HNF-1?, and various mutations are being reported.To help the overall understanding of MODY-related pathologic mutations, we studied a large MODY family found in 2012, in Shandong, China, which contained 9 patients over 3 generations. DNA was extracted from the periphery blood samples of (i) 9 affected members, (ii) 17 unaffected members, and (iii) 1000 healthy controls. Three pooled samples were obtained by mixing equal quantity of DNA of each individual within the each group. Totally 400 microsatellite markers across the whole genome were genotyped by capillary electrophoresis. The known MODY-related gene near the identified marker was sequenced to look for putative risk variants.Allelic frequency of marker D17S798 on chromosome 17q11.2 were significantly different (P<0.001) between the affected vs. unaffected members and the affected vs. healthy controls, but not between the unaffected members vs. healthy controls. MODY5-related gene, hepatocyte nuclear factor-1? (HNF-1?) on 17q12 near D17S798 became the candidate gene. A single nucleotide variant (SNV) of C77T in the non-coding area of exon 1 of HNF-1? was found to be related to MODY5.This novel SNV of HNF-1? contributes to the diabetes development in the family through regulating gene expression most likely. The findings help presymptomatic diagnosis, and imply that mutations in the non-coding areas, as well as in the exons, play roles in the etiology of MODY.

SUBMITTER: Zhou P

PROVIDER: S-EPMC4841871 | biostudies-literature | 2016 Feb

REPOSITORIES: biostudies-literature

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A Single Nucleotide Variant in HNF-1β is Associated with Maturity-Onset Diabetes of the Young in a Large Chinese Family.

Zhou Peng P Wei Ran R Guo Zhenkui Z Zhu Haining H Campbell Desmond D Li Qi Q Xu Xiaoqun X Wang Junfu J Luan Meng M Chen Xing X Chen Gang G

Iranian journal of public health 20160201 2

<h4>Background</h4>Maturity-onset diabetes of the young (MODY) is a heterogeneous entity of monogenic disorders characterized by autosomal dominant inheritance. Eleven genes were related, including HNF4α, GCK, HNF1α, IPF1, and HNF-1β, and various mutations are being reported.<h4>Methods</h4>To help the overall understanding of MODY-related pathologic mutations, we studied a large MODY family found in 2012, in Shandong, China, which contained 9 patients over 3 generations. DNA was extracted from ...[more]

PMID: 27114981

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Project description:BackgroundWe aimed to analyze a novel ABCC8 variant of a Chinese patient with suspected maturity-onset diabetes of the young (MODY) and to provide evidence for precise diagnosis and appropriate treatment.MethodA Chinese family with suspected MODY was recruited in this study, which included a 15-year-old female patient with diabetes. Clinical data and blood samples were collected from the proband and other family members. All of the living relatives were given an oral glucose tolerance test. Next-generation sequencing was performed to identify the mutated genes in the proband. Sanger sequencing was utilized to confirm the location of the pathogenic variant in all subjects. Further treatment was referred to targeted family members according to genetic testing.ResultsThe proband was found to have a random blood glucose level of 244.8 mg/dl and an HbA1c level of 9.2%. Before this investigation, her grandparents had been diagnosed with diabetes. The second uncle, two aunts, mother, and cousin of the proband were diagnosed with diabetes by abnormal HbA1C (6.5-12.1%) and fasting blood glucose (FBG, 91.4-189.7 mg/dl). The second aunt of the proband had impaired glucose homeostasis (HbA1C = 6.4% and FBG = 88.0 mg/dl). One novel missense variant c.1432G>A (p.A478T) in exon 9 of the ABCC8 gene was detected in the proband with suspected MODY. The variant was also found in six family members with diabetes or impaired glucose homeostasis, including her second uncle, two aunts, mother, and cousin. After the treatment was switched to glimepiride, the fasting blood glucose was adjusted to 99.54 mg/dl, the 2-h postprandial blood glucose was 153.54 mg/dl, serum fructosamine was 259 μmol/l, and HbA1c was 5.8%. The glycemic control remained optimal, and no hypoglycemic episodes were observed in the living relatives.ConclusionThis study revealed one novel missense variant of the ABCC8 gene in Chinese families. The present findings indicated that the members of this family responded to treatment with sulfonylureas as previously seen in ABCC8 MODY.

Dataset Information

A Single Nucleotide Variant in HNF-1? is Associated with Maturity-Onset Diabetes of the Young in a Large Chinese Family.

Publications

A Single Nucleotide Variant in HNF-1β is Associated with Maturity-Onset Diabetes of the Young in a Large Chinese Family.

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