A novel missense variant in the ATPase domain of ATP8A2 and review of phenotypic variability of ATP8A2-related disorders caused by missense changes.

ABSTRACT: ATPase, class 1, type 8 A, member 2 (ATP8A2) is a P4-ATPase with a critical role in phospholipid translocation across the plasma membrane. Pathogenic variants in ATP8A2 are known to cause cerebellar ataxia, impaired intellectual development, and disequilibrium syndrome 4 (CAMRQ4) which is often associated with encephalopathy, global developmental delay, and severe motor deficits. Here, we present a family with two siblings born from a consanguineous, first-cousin union from Sudan presenting with global developmental delay, intellectual disability, spasticity, ataxia, nystagmus, and thin corpus callosum. Whole exome sequencing revealed a homozygous missense variant in the nucleotide binding domain of ATP8A2 (p.Leu538Pro) that results in near complete loss of protein expression. This is in l

SUBMITTER: Flannery KP 

PROVIDER: S-EPMC11534842 | biostudies-literature | 2024 Oct

REPOSITORIES: biostudies-literature