Biallelic Truncation Variants in Atp9a Are Associated With a Novel Autosomal Recessive Neurodevelopmental Disorder Publisher



Mattioli F¹ ; Darvish H² ; Paracha SA³ ; Tafakhori A⁴ ; Firouzabadi SG⁵ ; Chapi M⁴ ; Baig HMA⁶ ; Reymond A¹ ; Antonarakis SE^{7, 8} ; Ansar M^{7, 9, 10} Show Affiliations
Source: npj Genomic Medicine Published:2021

Abstract

Intellectual disability (ID) is a highly heterogeneous disorder with hundreds of associated genes. Despite progress in the identification of the genetic causes of ID following the introduction of high-throughput sequencing, about half of affected individuals still remain without a molecular diagnosis. Consanguineous families with affected individuals provide a unique opportunity to identify novel recessive causative genes. In this report, we describe a novel autosomal recessive neurodevelopmental disorder. We identified two consanguineous families with homozygous variants predicted to alter the splicing of ATP9A which encodes a transmembrane lipid flippase of the class II P4-ATPases. The three individuals homozygous for these putatively truncating variants presented with severe ID, motor and speech impairment, and behavioral anomalies. Consistent with a causative role of ATP9A in these patients, a previously described Atp9a−/− mouse model showed behavioral changes. © 2021, The Author(s).