Abstract
We report the clinical and biochemical findings from two unrelated patients who presented with a novel syndrome: encephalopathy, intellectual disability, severe hypotonia, chorea and optic atrophy. Whole exome sequencing (WES) uncovered a homozygous mutation in the ATP8A2 gene (NM_016529:c.1287G > T, p.K429N) in one patient and compound heterozygous mutations (c.1630G > C, p.A544P and c.1873C > T, p.R625W) in the other. Only one haploinsufficiency case and a family with a homozygous mutation in ATP8A2 gene (c.1128C > G, p.I376M) have been described so far, with phenotypes that differed slightly from the patients described herein. In conclusion, our data expand both the genetic and phenotypic spectrum associated with ATP8A2 gene mutations.
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Acknowledgments
The authors thank the patients and their families for their contribution. Also, we would like to thank Alicia Torrado for the valuable comments on the manuscript. This work was supported by the Spanish Instituto de Salud Carlos III (ISCIII) and European Regional Development Fund (ERDF) (grant PI10/00063 and PI14/00790 to F.M-A., and PI12/01683 to MA.M.).
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Written informed consent was obtained from the patients’ parents, and the Ethic Committee of the Instituto de Investigación Hospital 12 de Octubre (i+12) approved the study.
Web resources
The URLs for the data presented here are as follows:
OMIM, http://www.omim.org/
SIFT, http://sift.jcvi.org/
Polyphen-2, http://genetics.bwh.harvard.edu/pph2/
MutPred, http://mutpred.mutdb.org/
Mutation Taster, http://www.mutationtaster.org/
1000G, http://www.1000genomes.org/
EVS, http://evs.gs.washington.edu/EVS/
ExAC Browser, http://exac.broadinstitute.org
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Elena Martín-Hernández and María Elena Rodríguez-García contributed equally to this work.
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Martín-Hernández, E., Rodríguez-García, M.E., Camacho, A. et al. New ATP8A2 gene mutations associated with a novel syndrome: encephalopathy, intellectual disability, severe hypotonia, chorea and optic atrophy. Neurogenetics 17, 259–263 (2016). https://doi.org/10.1007/s10048-016-0496-y
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DOI: https://doi.org/10.1007/s10048-016-0496-y