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

backgroundMitral 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.

methodsWe 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.

resultsComplete 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.

conclusionsOur 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.