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

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 <italic>EPS15L1</italic> gene located on chromosome 19p13.11. This is the first biallelic variant identified in the <italic>EPS15L1</italic> gene underlying SHFM. Our findings report the first direct involvement of <italic>EPS15L1</italic> gene in the development of human limbs. [ABSTRACT FROM AUTHOR]