Journal
NATURE GENETICS
Volume 44, Issue 9, Pages 1030-+Publisher
NATURE PUBLISHING GROUP
DOI: 10.1038/ng.2358
Keywords
-
Categories
Funding
- Italian Patient Association for Alternating Hemiplegia (AISEA Onlus)
- Center for Human Genome Variation
- Center for HIV/AIDS Vaccine Immunology
- Joseph and Kathleen Bryan Alzheimer's Disease Research Center from the National Institutes of Health (NIH), including the National Institute of Allergy and Infectious Disease [UO1AIO67854]
- National Institute on Aging [P30 AG028377]
- National Institute of Neurological Disorders and Stroke [RC2NS070344, 1RC2NS070342-01]
- National Institute of Mental Health [RC2MH089915]
- AHCF
- ENRAH for SMEs Consortium under the European Commission Sixth Framework Programme
- Institut National de la Sante et de la Recherche Medicale
- Centre National de la Recherche Scientifique
- University Pierre and Marie Curie
- Association Francaise Contre les Myopathies
- Association Francaise de l'Hemiplegie Alternante
- AISEA Onlus
- Wellcome Trust [084730]
- National Center for Research Resources [UL1RR025764]
- NIH [1T32HL105321-01]
- University of Luxembourg Institute for Systems Biology Program
- Center for Medical Systems Biology established in The Netherlands Genomics Initiative and The Netherlands Organisation for Scientific Research [050-060-409]
- Contrat d'Interface from Assistance Publique-Hopitaux de Paris
Ask authors/readers for more resources
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.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available