NPJ Genom Med.: auth.: group Reymond

NPJ Genom Med. 2021 Nov 11;6(1):94. doi: 10.1038/s41525-021-00255-z.

Biallelic truncation variants in ATP9A are associated with a novel autosomal recessive neurodevelopmental disorder

Francesca Mattioli # 1Hossein Darvish # 2Sohail Aziz Paracha 3Abbas Tafakhori 4Saghar Ghasemi Firouzabadi 5Marjan Chapi 4Hafiz Muhammad Azhar Baig 6Alexandre Reymond 7Stylianos E Antonarakis 8 9Muhammad Ansar 10 11 12


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.