First direct evidence of involvement of a homozygous loss‐of‐function variant in the EPS15L1 gene underlying split‐hand/split‐foot malformation

2017/10/10 by M. Umair, Muhammad Umair, A. Ullah +8
Biochemistry, Genetics and Molecular Biology · Medicine · #Congenital limb and hand anomalies #Genomic variations and chromosomal abnormalities #Prenatal Screening and Diagnostics

paper · pdf · doi:10.1111/cge.13152

openalex publication_date 2017/10/10 · crossref created 2017/10/10 · openalex created_date 2017/10/20 · crossref issued 2018/01/25 · crossref published 2018/01/25 · crossref published-online 2018/01/25 · crossref published-print 2018/03/01 · crossref deposited 2023/09/25 · crossref indexed 2026/07/28 · openalex updated_date 2026/07/29

Abstract

Split-hand/split-foot malformation (SHFM) is a severe form of congenital limb deformity characterized by the absence of 1 or more digits and/or variable degree of median clefts of hands and feet. The present study describes an investigation of a consanguineous family of Pakistani origin segregating SHFM in an autosomal recessive manner. Human genome scan using SNP markers followed by whole exome sequencing revealed a frameshift deletion (c.409delA, p.Ser137Alafs*19) in the EPS15L1 gene located on chromosome 19p13.11. This is the first biallelic variant identified in the EPS15L1 gene underlying SHFM. Our findings report the first direct involvement of EPS15L1 gene in the development of human limbs.

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