Genetic and Functional Analyses of the Novel KLF11 Pro193Thr Variant in a Three-Generation Family with MODY7
Horm Metab Res DOI: 10.1055/a-1961-6281KLF11 regulates insulin gene expression through binding to the insulin promoter
and has been reported as a causative gene for maturity-onset diabetes of the
young 7 (MODY7). Here, we report a novel KLF11 variant associated with a
three-generation family with early childhood-onset diabetes and explore its
clinical and functional characteristics. The three-generational pedigree
contains five patients affected by diabetes. The pathogenic variant identified
by whole-exome sequencing was further confirmed by Sanger sequencing and
pedigree verification. Luciferase reporter assays and glucose-stimulated insulin
secretion were used to examine whether the KLF11 variant binds to the insulin
promoter and regulate insulin secretion in vitro. The proband, his son, and his
uncle exhibited hyperglycemia at ages 32, 13 and 71 years, respectively. All
three patients showed characteristics of metabolic syndrome (obesity,
dyslipidemia, and diabetes), but the insulin secretion of islet β-cells
was impaired. A novel heterozygous missense variant, c.577 C>A
(p.Pro193Thr) of the KLF11 gene was detected in all three patients. This variant
co-segregates with the diabetes phenotype, consistent with an autosomal dominant
disorder. The identified KLF11 p.Pro193Thr variant drastically decreased the
...
Source: Hormone and Metabolic Research - Category: Endocrinology Authors: Guan, Gaopeng Qin, Tiantian Zhao, Li-ling Jin, Ping Tags: Original Article: Endocrine Research Source Type: research
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