PIEZO1 loss of function compound heterozygous mutation in the rare congenital human disorder Prune Belly Syndrome

Prune Belly Syndrome (PBS) is a rare congenital myopathy that is incompletely understood genetically. In this IRB approved study, one white Non-Hispanic 35 year-old male PBS proband was prospectively enrolled and phenotyped. Blood lymphocyte DNA from the proband underwent paired-end Whole Exome Sequencing using the Illumina SureSelect kit and HiSeq2500 sequencer with data pipeline analysis. Variants were filtered for rare minor allele frequency and type (splice site, nonsense or missense), validated by Sanger sequencing, and confirmed variants had inheritance analysis on available samples. Our WES analysis identified novel compound heterozygous variants in the PIEZO1 gene. We conducted an extensive functional analysis of the PIEZO1 PBS variants that revealed loss-of-function... (for more see dbGaP study page.)