Abstract
Mitral valve prolapse (MVP) is one of the most common valvular
abnormalities and has been suggested to have a significant hereditary
component. However, only few causative genes have been identified
(FLNA , DCHS1 , DZIP1 and PLD1 ) so far. We
report a family with MVP in which a missense variant in thePDLIM7 gene was identified based on whole exome sequence analysis
that co-segregated with the phenotype. The frequency of the variant was
very rare in the population database GnomAD (0.0012%) and involved a
moderately conserved nucleotide (PhyloP 3.68) and amino acid
(considering 12 species); most of the functional annotation algorithms
predicted a deleterious effect of the mutation. The Pdlim7 protein is a
member of the PDZ-LIM family and previous studies showed that its loss
of function in zebrafish leads to Tbx5 independent misregulation of the
actin cytoskeleton, resulting in cardiac abnormalities including MV
malformations. Also, Pdlim7 knock-out mice showed an increased MV
annulus diameter compared to wild-type mice. These results suggestPDLIM7 as a possible novel candidate gene for familial MVP.