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

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...

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Autores principales:	Francesca Mattioli, Hossein Darvish, Sohail Aziz Paracha, Abbas Tafakhori, Saghar Ghasemi Firouzabadi, Marjan Chapi, Hafiz Muhammad Azhar Baig, Alexandre Reymond, Stylianos E. Antonarakis, Muhammad Ansar
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2021
Materias:	Medicine R Genetics QH426-470
Acceso en línea:	https://doaj.org/article/400519f225054fa7a452b59040f859dd
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spelling	oai:doaj.org-article:400519f225054fa7a452b59040f859dd2021-11-14T12:44:41ZBiallelic truncation variants in ATP9A are associated with a novel autosomal recessive neurodevelopmental disorder10.1038/s41525-021-00255-z2056-7944https://doaj.org/article/400519f225054fa7a452b59040f859dd2021-11-01T00:00:00Zhttps://doi.org/10.1038/s41525-021-00255-zhttps://doaj.org/toc/2056-7944Abstract 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.Francesca MattioliHossein DarvishSohail Aziz ParachaAbbas TafakhoriSaghar Ghasemi FirouzabadiMarjan ChapiHafiz Muhammad Azhar BaigAlexandre ReymondStylianos E. AntonarakisMuhammad AnsarNature PortfolioarticleMedicineRGeneticsQH426-470ENnpj Genomic Medicine, Vol 6, Iss 1, Pp 1-5 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Genetics QH426-470
spellingShingle	Medicine R Genetics QH426-470 Francesca Mattioli Hossein Darvish Sohail Aziz Paracha Abbas Tafakhori Saghar Ghasemi Firouzabadi Marjan Chapi Hafiz Muhammad Azhar Baig Alexandre Reymond Stylianos E. Antonarakis Muhammad Ansar Biallelic truncation variants in ATP9A are associated with a novel autosomal recessive neurodevelopmental disorder
description	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.
format	article
author	Francesca Mattioli Hossein Darvish Sohail Aziz Paracha Abbas Tafakhori Saghar Ghasemi Firouzabadi Marjan Chapi Hafiz Muhammad Azhar Baig Alexandre Reymond Stylianos E. Antonarakis Muhammad Ansar
author_facet	Francesca Mattioli Hossein Darvish Sohail Aziz Paracha Abbas Tafakhori Saghar Ghasemi Firouzabadi Marjan Chapi Hafiz Muhammad Azhar Baig Alexandre Reymond Stylianos E. Antonarakis Muhammad Ansar
author_sort	Francesca Mattioli
title	Biallelic truncation variants in ATP9A are associated with a novel autosomal recessive neurodevelopmental disorder
title_short	Biallelic truncation variants in ATP9A are associated with a novel autosomal recessive neurodevelopmental disorder
title_full	Biallelic truncation variants in ATP9A are associated with a novel autosomal recessive neurodevelopmental disorder
title_fullStr	Biallelic truncation variants in ATP9A are associated with a novel autosomal recessive neurodevelopmental disorder
title_full_unstemmed	Biallelic truncation variants in ATP9A are associated with a novel autosomal recessive neurodevelopmental disorder
title_sort	biallelic truncation variants in atp9a are associated with a novel autosomal recessive neurodevelopmental disorder
publisher	Nature Portfolio
publishDate	2021
url	https://doaj.org/article/400519f225054fa7a452b59040f859dd
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Biallelic truncation variants in ATP9A are associated with a novel autosomal recessive neurodevelopmental disorder

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