@article{be45d4e5704e437c8279e94901c7b877,
title = "De novo mutations in ATP1A3 cause alternating hemiplegia of childhood",
abstract = "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.",
keywords = "Adult, Animals, COS Cells, Cercopithecus aethiops, Child, Family, Female, Genetic Predisposition to Disease, HeLa Cells, Hemiplegia, High-Throughput Nucleotide Sequencing, Humans, Male, Models, Biological, Mutation, Pedigree, Protein Structure, Secondary, Sodium-Potassium-Exchanging ATPase",
author = "Heinzen, {Erin L} and Swoboda, {Kathryn J} and Yuki Hitomi and Fiorella Gurrieri and Sophie Nicole and {de Vries}, Boukje and Tiziano, {F Danilo} and Bertrand Fontaine and Walley, {Nicole M} and Sin{\'e}ad Heavin and Eleni Panagiotakaki and Stefania Fiori and Emanuela Abiusi and {Di Pietro}, Lorena and Sweney, {Matthew T} and Newcomb, {Tara M} and Louis Viollet and Chad Huff and Jorde, {Lynn B} and Reyna, {Sandra P} and Murphy, {Kelley J} and Shianna, {Kevin V} and Gumbs, {Curtis E} and Latasha Little and Kenneth Silver and Pt{\'a}{\v c}ek, {Louis J} and Joost Haan and Ferrari, {Michel D} and Bye, {Ann M} and Herkes, {Geoffrey K} and Whitelaw, {Charlotte M} and David Webb and Lynch, {Bryan J} and Peter Uldall and King, {Mary D} and Scheffer, {Ingrid E} and Giovanni Neri and Alexis Arzimanoglou and {van den Maagdenberg}, {Arn M J M} and Sisodiya, {Sanjay M} and Mikati, {Mohamad A} and Goldstein, {David B} and {European Alternating Hemiplegia of Childhood (AHC) Genetics Consortium}",
year = "2012",
doi = "10.1038/ng.2358",
language = "English",
volume = "44",
pages = "1030--4",
journal = "Nature Genetics",
issn = "1061-4036",
publisher = "Nature Publishing Group",
number = "9",
}