Report of a rare case of congenital mitral valve prolapse with chronic kidney disease-reconsidered genotype-phenotypic correlations

Sun，Liping; Zhang，Xinzhou

2021

10.1002/mgg3.1558

MOLECULAR GENETICS & GENOMIC MEDICINE   影响因子和分区

2324-9269

["Background: Mitral valve prolapse (MVP) is a common cardiovascular disease defined as a late systolic click or mitral valve lobes that move up into the left atrium during ventricular systole, with or without mitral insufficiency. Dachsous catherin-related 1 (DCHS1) is one of the two known pathogenic genes associated with MVP. However, there is little information about the renal dysfunction caused by MVP and DCHS1 mutations.","Methods: We analyzed the genetic etiology in a rare case of 9-year-old boy affected by chronic renal failure with MVP. Subsequently, we constructed stable cell lines overexpressing wild-type DCHS1 or mutant DCHS1 (c.8309G>A, p.R2770Q) to evaluate the influence of the DCHS1 mutation on the proliferation, apoptosis, and autophagy.","Results: Complete exome sequencing and pedigree verification revealed a mutation p.R2770Q (c.8309G>A) in exon 21 of the DCHS1 gene carried by the patient, which may affect the DNA binding. No such mutation was detected in his parents, indicating that this was a new mutation. Potential functional impact of sequence variants was predicted using in silico prediction programs including SIFT, Polyphen2, and Condel. This variant was determined to be a pathogenic mutation that has not been reported elsewhere. Subsequently, we used a stable DCHS1 gene-mutated HK-2 cell line to analyse proliferation, apoptosis, and autophagy, showed that kidney volume decreased with increasing cell death associated with a reduced proliferation.","Conclusions: Our analysis revealed a heterozygous variation of DCHS1 in a child with MVP. Our observations highlight previously unrecognized phenotypes of the currently recognized MVP genotype, including distinct chronic renal failure."]

chronic renal failure DCHS1 mutation genotype-phenotype correlations mitral valve prolapse

SCI

英语

第一 ; 通讯

Youth Research Cadre Cultivation Project of Shenzhen People's Hospital[SYKYPY201904] ; Guangdong Science and Technology Project, China[A2019416]

Genetics & Heredity

Genetics & Heredity

WOS:000884222800014

WILEY

Web of Science

Shenzhen Key Laboratory of Renal,Department of Nephrology,Shenzhen People’s Hospital (The Second Clinical Medical College,Jinan University; The First Affiliated Hospital,Southern University of Science and Technology),Shenzhen,China

Sun，Liping,Zhang，Xinzhou. Report of a rare case of congenital mitral valve prolapse with chronic kidney disease-reconsidered genotype-phenotypic correlations[J]. MOLECULAR GENETICS & GENOMIC MEDICINE,2021,9(1).

Sun，Liping,&Zhang，Xinzhou.(2021).Report of a rare case of congenital mitral valve prolapse with chronic kidney disease-reconsidered genotype-phenotypic correlations.MOLECULAR GENETICS & GENOMIC MEDICINE,9(1).

Sun，Liping,et al."Report of a rare case of congenital mitral valve prolapse with chronic kidney disease-reconsidered genotype-phenotypic correlations".MOLECULAR GENETICS & GENOMIC MEDICINE 9.1(2021).