De novo mutations in ATP1A3 cause alternating hemiplegia of childhood

Erin L. Heinzen; Kathryn J. Swoboda; Yuki Hitomi; Fiorella Gurrieri; Sophie Nicole; Boukje de Vries; F. Danilo Tiziano; Bertrand Fontaine; Nicole M. Walley; Sinead Heavin; Eleni Panagiotakaki; Stefania Fiori; Emanuela Abiusi; Lorena Di Pietro; Matthew T. Sweney; Tara M. Newcomb; Louis Viollet; Chad Huff; Lynn B. Jorde; Sandra P. Reyna; Kelley J. Murphy; Kevin V. Shianna; Curtis E. Gumbs; Latasha Little; Kenneth Silver; Louis J. Ptacek; Joost Haan; Michel D. Ferrari; Ann M. Bye; Geoffrey K. Herkes; Charlotte M. Whitelaw; David Webb; Bryan J. Lynch; Peter Uldall; Mary D. King; Ingrid E. Scheffer; Giovanni Neri; Alexis Arzimanoglou; Arn M. J. M. van den Maagdenberg; Sanjay M. Sisodiya; Mohamad A. Mikati; David B. Goldstein; European Alternating Hemiplegia

doi:10.1038/ng.2358

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De novo mutations in ATP1A3 cause alternating hemiplegia of childhood

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De novo mutations in ATP1A3 cause alternating hemiplegia of childhood

Erin L. Heinzen, Kathryn J. Swoboda, Yuki Hitomi, Fiorella Gurrieri, Sophie Nicole, Boukje de Vries, F. Danilo Tiziano, Bertrand Fontaine, Nicole M. Walley, Sinead Heavin, …

Nature genetics, Vol.44(9), pp.1030-1034

01/09/2012

DOI: https://doi.org/10.1038/ng.2358

PMID: 22842232

Résumé

Genetics & Heredity

Life Sciences & Biomedicine

Science & Technology

Alternating hemiplegia of childhood (AHC) is a rare, severe neurodevelopmental syndrome characterized by recurrent hemiplegic episodes and distinct neurological manifestations. AHC is usually a sporadic disorder and has unknown etiology. We used exome sequencing of seven patients with AHC and their unaffected parents to identify de novo nonsynonymous mutations in ATP1A3 in all seven individuals. In a subsequent sequence analysis of ATP1A3 in 98 other patients with AHC, we found that ATP1A3 mutations were likely to be responsible for at least 74% of the cases; we also identified one inherited mutation in a case of familial AHC. Notably, most AHC cases are caused by one of seven recurrent ATP1A3 mutations, one of which was observed in 36 patients. Unlike ATP1A3 mutations that cause rapid-onset dystonia-parkinsonism, AHC-causing mutations in this gene caused consistent reductions in ATPase activity without affecting the level of protein expression. This work identifies de novo ATP1A3 mutations as the primary cause of AHC and offers insight into disease pathophysiology by expanding the spectrum of phenotypes associated with mutations in ATP1A3.

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Titre: De novo mutations in ATP1A3 cause alternating hemiplegia of childhood
Créateurs - sans rôle: Erin L. Heinzen - Duke University
Kathryn J. Swoboda - University of Utah
Yuki Hitomi - Duke Univ, Sch Med, Ctr Human Genome Variat, Durham, NC 27708 USA
Fiorella Gurrieri - Univ Cattolica Sacro Cuore, Inst Med Genet, Policlin A Gemelli, Rome, Italy
Sophie Nicole - Univ Paris 06, Ctr Rech, Inst Cerveau & Moelle Epiniere, UMR S975, Paris, France
Boukje de Vries - Leiden Univ, Med Ctr, Dept Human Genet, Leiden, Netherlands
F. Danilo Tiziano - Univ Cattolica Sacro Cuore, Inst Med Genet, Policlin A Gemelli, Rome, Italy
Bertrand Fontaine - Univ Paris 06, Ctr Rech, Inst Cerveau & Moelle Epiniere, UMR S975, Paris, France
Nicole M. Walley - Duke University
Sinead Heavin - Univ Melbourne, Austin Hlth, Dept Med, Melbourne, Vic, Australia
Eleni Panagiotakaki - Univ Hosp Lyon HCL, Woman Mother Child Hosp, Epilepsy Sleep & Pediat Neurophysiol Dept, Lyon, France
Stefania Fiori - Univ Cattolica Sacro Cuore, Inst Med Genet, Policlin A Gemelli, Rome, Italy
Emanuela Abiusi - Univ Cattolica Sacro Cuore, Inst Med Genet, Policlin A Gemelli, Rome, Italy
Lorena Di Pietro - Univ Cattolica Sacro Cuore, Inst Med Genet, Policlin A Gemelli, Rome, Italy
Matthew T. Sweney - Univ Utah, Dept Pediat, Salt Lake City, UT USA
Tara M. Newcomb - Univ Utah, Dept Pediat, Salt Lake City, UT USA
Louis Viollet - Univ Utah, Dept Neurol, Salt Lake City, UT USA
Chad Huff - Univ Utah, Eccles Inst Human Genet, Dept Human Genet, Salt Lake City, UT USA
Lynn B. Jorde - Univ Utah, Eccles Inst Human Genet, Dept Human Genet, Salt Lake City, UT USA
Sandra P. Reyna - Univ Utah, Dept Neurol, Salt Lake City, UT USA
Kelley J. Murphy - Univ Utah, Dept Neurol, Salt Lake City, UT USA
Kevin V. Shianna - Duke Univ, Sch Med, Ctr Human Genome Variat, Durham, NC 27708 USA
Curtis E. Gumbs - Duke Univ, Sch Med, Ctr Human Genome Variat, Durham, NC 27708 USA
Latasha Little - Duke Univ, Sch Med, Ctr Human Genome Variat, Durham, NC 27708 USA
Kenneth Silver - Univ Chicago, Dept Neurol, Comer Childrens Hosp, Chicago, IL 60637 USA
Louis J. Ptacek - Univ Calif San Francisco, Dept Neurol, San Francisco, CA USA
Joost Haan - Rijnland Hosp, Dept Neurol, Leiderdorp, Netherlands
Michel D. Ferrari - Leiden University
Ann M. Bye - Sydney Childrens Hosp, Dept Paediat Neurol, Randwick, NSW, Australia
Geoffrey K. Herkes - Univ Sydney, Royal N Shore Hosp, Sydney, NSW 2006, Australia
Charlotte M. Whitelaw - Univ Sydney, No Clin Sch, Sydney, NSW 2006, Australia
David Webb - Our Ladys Childrens Hosp, Dublin, Ireland
Bryan J. Lynch - Childrens Univ Hosp, Dublin, Ireland
Peter Uldall - Univ Copenhagen, Rigshosp, Dept Paediat & Adolescent Med, DK-2100 Copenhagen, Denmark
Mary D. King - Childrens Univ Hosp, Dublin, Ireland
Ingrid E. Scheffer - The University of Melbourne
Giovanni Neri - Univ Cattolica Sacro Cuore, Inst Med Genet, Policlin A Gemelli, Rome, Italy
Alexis Arzimanoglou - Univ Hosp Lyon HCL, Woman Mother Child Hosp, Epilepsy Sleep & Pediat Neurophysiol Dept, Lyon, France
Arn M. J. M. van den Maagdenberg - Leiden University
Sanjay M. Sisodiya - UCL, Inst Neurol, Dept Clin & Expt Epilepsy, London, England
Mohamad A. Mikati - Duke University
David B. Goldstein - Duke Univ, Sch Med, Ctr Human Genome Variat, Durham, NC 27708 USA
European Alternating Hemiplegia
Détails de publication: Nature genetics, Vol.44(9), pp.1030-1034
Éditeur: Springer Nature
Nombre de pages: 6
Note de subvention: Association Francaise Contre les Myopathies; Association Francaise contre les Myopathies University of Luxembourg Institute for Systems Biology Program UL1RR025764 / National Center for Research Resources; United States Department of Health & Human Services; National Institutes of Health (NIH) - USA; NIH National Center for Research Resources (NCRR) Center for HIV/AIDS Vaccine Immunology Institut National de la Sante et de la Recherche Medicale; Institut National de la Sante et de la Recherche Medicale (Inserm) 050-060-409 / Center for Medical Systems Biology established in The Netherlands Genomics Initiative and The Netherlands Organisation for Scientific Research Center for Human Genome Variation University Pierre and Marie Curie RC2NS070344; 1RC2NS070342-01 / National Institute of Neurological Disorders and Stroke; United States Department of Health & Human Services; National Institutes of Health (NIH) - USA; NIH National Institute of Neurological Disorders & Stroke (NINDS) AHCF
Identifiants: 99139451909311
Unité académique: Institut de Génomique Fonctionnelle - IGF
Langue: English
Type de ressource: Journal article