Sequence Variants in the WNT10B and TP63 Genes Underlying Isolated Split-Hand/Split-Foot Malformation.
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.  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.  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.  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.
['Bilal|Muhammad|M|', 'Hayat|Amir|A|', 'Umair|Muhammad|M|', 'Ullah|Asmat|A|', 'Khawaja|Sundus|S|', 'Malik|Erum|E|', 'Burmeister|Margit|M|', 'Bibi|Nousheen|N|', 'Umm-E-Kalsoom|||', 'Memon|Muhammad Iqbal|MI|', 'Basit|Sulman|S|', 'Ahmad|Wasim|W|', 'Khan|Bushra|B|']
D000328:Adult D002648:Child D002675:Child, Preschool D005190:Family D005260:Female D056726:Genetic Association Studies D005838:Genotype D006579:Heterozygote D006720:Homozygote D006801:Humans D017880:Limb Deformities, Congenital D008297:Male D008875:Middle Aged D020125:Mutation, Missense D010154:Pakistan D010375:Pedigree D010641:Phenotype D011518:Proto-Oncogene Proteins D014157:Transcription Factors D025521:Tumor Suppressor Proteins D000073359:Whole Exome Sequencing D051153:Wnt Proteins D055815:Young Adult
WNT10B TP63 SHFM disease causing variants