Homozygous <i>CHST11</i> mutation in chondrodysplasia, brachydactyly, overriding digits, clino-symphalangism and synpolydactyly

Abstract

The limb malformations include brachydactyly, overriding digits and clino-symphalangism in hands and feet and syndactyly and hexadactyly in feet. Skeletal defects include scoliosis, dislocated patellae and fibulae and pectus excavatum. The disease locus is mapped to a 1.6 Mb region at 12q23, harbouring a homozygous in-frame deletion of 15 nucleotides in <i>CHST11.</i> Novel variant c.467_481del (p.L156_N160del) is deduced to lead to the deletion of five evolutionarily highly conserved amino acids and predicted as damaging to protein by in silico analysis. Our findings confirm the crucial role of CHST11 in skeletal morphogenesis and show that <i>CHST11</i> defects have variable manifestations that include a variety of limb malformations and skeletal defects.