A novel frameshift variant in UBA2 causing split-hand/foot malformations in a Pakistani family

Abstract

AbstractSplit-hand/foot malformation (SHFM) shows diverse heterogeneity and manifests with reduced penetrance and variable expressivity. This study investigated the underlying genetic cause of a family segregating SHFM. Exome sequencing followed by Sanger sequencing identified a novel single nucleotide heterozygous variant (NC_000019.9 (NM_005499.3):c.1118del) in UBA2 cosegregating in the family in an autosomal dominant manner. Our findings conclude that reduced penetrance and variable expressivity are the two remarkable and unusual features of SHFM.