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

Autor:	Mattioli F; Center for Integrative Genomics, University of Lausanne, Lausanne, Switzerland., Darvish H; Neuroscience Research Center, Faculty of Medicine, Golestan University of Medical Sciences, Gorgan, Iran., Paracha SA; Anatomy Department, Khyber Medical University Institute of Medical Sciences (KIMS), Kohat, Pakistan., Tafakhori A; Iranian Center of Neurological Research, Neuroscience Institute, Tehran University of Medical Sciences, Tehran, Iran., Firouzabadi SG; Genetics Research Center, University of Social Welfare and Rehabilitation Sciences, Tehran, Iran., Chapi M; Iranian Center of Neurological Research, Neuroscience Institute, Tehran University of Medical Sciences, Tehran, Iran., Baig HMA; Department of Biotechnology, Institute of Biochemistry, Biotechnology and Bioinformatics, The Islamia University of Bahawalpur, Bahawalpur, Pakistan., Reymond A; Center for Integrative Genomics, University of Lausanne, Lausanne, Switzerland. alexandre.reymond@unil.ch., Antonarakis SE; Department of Genetic Medicine and Development, University of Geneva Medical Faculty, Geneva, 1211, Switzerland. stylianos.antonarakis@unige.ch.; Medigenome, Swiss Institute of Genomic Medicine, Geneva, Switzerland. stylianos.antonarakis@unige.ch., Ansar M; Department of Genetic Medicine and Development, University of Geneva Medical Faculty, Geneva, 1211, Switzerland.; Jules-Gonin Eye Hospital, Department of Ophthalmology, University of Lausanne, 1004, Lausanne, Switzerland.; Institute of Molecular and Clinical Ophthalmology Basel (IOB), Basel, Switzerland.
Jazyk:	angličtina
Zdroj:	NPJ genomic medicine [NPJ Genom Med] 2021 Nov 11; Vol. 6 (1), pp. 94. Date of Electronic Publication: 2021 Nov 11.
DOI:	10.1038/s41525-021-00255-z
Abstrakt:	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).)
Databáze:	MEDLINE
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