ACLASP1variant suggests a phenotypic relation with lissencephaly in humans

Abstract

Lissencephaly is a severe brain developmental disorder; characterized by reduced brain folding due to defective neuronal migration. This study investigates the genetic basis of lissencephaly in a consanguineous family, focusing on theCLASP1gene. Whole-exome sequencing identified a novel homozygous variant (c.4442G>A p.(Arg1481His)) inCLASP1. Clinical evaluation revealed severe developmental delays, microcephaly, seizures, and lissencephaly in the affected siblings. The variant was heterozygous in the healthy parents and a heterozygous carrier in an unaffected sibling. This study underscores the role of CLASP1 in brain development and suggests that the identified variant disrupts CLASP1 interaction with the microtubule cytoskeleton, contributing to lissencephaly pathogenesis.