{Reference Type}: Case Reports
{Title}: Sequence Variants in the WNT10B and TP63 Genes Underlying Isolated Split-Hand/Split-Foot Malformation.
{Author}: Bilal M;Hayat A;Umair M;Ullah A;Khawaja S;Malik E;Burmeister M;Bibi N;Umm-E-Kalsoom ;Memon MI;Basit S;Ahmad W;Khan B;
{Journal}: Genet Test Mol Biomarkers
{Volume}: 24
{Issue}: 9
{Year}: Sep 2020
{Factor}: 1.736
{DOI}: 10.1089/gtmb.2020.0024
{Abstract}: Aims: Split-hand/split-foot malformation (SHFM) is a developmental and congenital limb malformation characterized by variable degrees of medial clefting or absence of one or more digits in hands and/or feet. The aim of this study was to identify the underlying cause of three consanguineous Pakistani families showing various types of SHFM-related features. Materials and Methods: Standard molecular methods, including whole-genome sequencing (WGS), whole-exome sequencing (WES), microsatellite markers-based genotyping, and Sanger sequencing were performed to search for the likely causative variants. Results: In family A, WES revealed a novel homozygous missense variant [c.338G>A, p.(Gly113Asp)] in the WNT10B gene. In family B, microsatellite-based genotyping followed by Sanger sequencing revealed a novel homozygous 13 base pairs deletion [c.884-896delTCCAGCCCCGTCT, p.(Phe295Cysfs*87)] in the same gene. In family C, WGS divulged a previously reported heterozygous missense variant [c.956G>A, p.(Arg319His)] in the TP63 gene. Conclusions: Mapping and sequencing genes and variants for severe skeletal disorders, such as SHRM, will facilitate establishing specific genotype-phenotype correlations and providing genetic counseling for the families suffering from such conditions.