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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 SE7, 8 ; Ansar M7, 9, 10
Authors

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).
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