Format

Send to

Choose Destination
J Child Neurol. 2015 Nov;30(13):1749-56. doi: 10.1177/0883073815579708. Epub 2015 Apr 20.

CAOS-Episodic Cerebellar Ataxia, Areflexia, Optic Atrophy, and Sensorineural Hearing Loss: A Third Allelic Disorder of the ATP1A3 Gene.

Author information

1
Pediatric Neurology Unit, Edmond and Lily Children's Hospital, The Chaim Sheba Medical Center, Ramat Gan, Israel The Pinchas Borenstein Talpiot Medical Leadership Program, The Chaim Sheba Medical Center, Ramat Gan, Israel Galih.md@gmail.com.
2
Program in Genetics and Genome Biology, The Hospital for Sick Children, Toronto, Ontario, Canada.
3
Division of Neurology, Department of Pediatrics, The Hospital for Sick Children, and University of Toronto, Toronto, Ontario, Canada.
4
Center for Biomedical Informatics, Harvard Medical School, Boston, MA, USA.
5
Pediatric Neurology Unit, Edmond and Lily Children's Hospital, The Chaim Sheba Medical Center, Ramat Gan, Israel.
6
Metabolic Disease Unit, Edmond and Lily Children's Hospital, the Chaim Sheba Medical Center, Ramat Gan, Israel.
7
Metabolic Disease Unit, Edmond and Lily Children's Hospital, the Chaim Sheba Medical Center, Ramat Gan, Israel The Sackler School of Medicine, Tel Aviv University, Tel Aviv, Israel.
8
Program in Genetics and Genome Biology, The Hospital for Sick Children, Toronto, Ontario, Canada Division of Neurology, Department of Pediatrics, The Hospital for Sick Children, and University of Toronto, Toronto, Ontario, Canada.
9
Pediatric Neurology Unit, Edmond and Lily Children's Hospital, The Chaim Sheba Medical Center, Ramat Gan, Israel The Sackler School of Medicine, Tel Aviv University, Tel Aviv, Israel.

Abstract

We describe the molecular basis of a distinctive syndrome characterized by infantile stress-induced episodic weakness, ataxia, and sensorineural hearing loss, with permanent areflexia and optic nerve pallor. Whole exome sequencing identified a deleterious heterozygous c.2452 G>A, p.(E818K) variant in the ATP1A3 gene and structural analysis predicted its protein-destabilizing effect. This variant has not been reported in context with rapid-onset dystonia parkinsonism and alternating hemiplegia of childhood, the 2 main diseases associated with ATP1A3. The clinical presentation in the family described here differs categorically from these diseases in age of onset, clinical course, cerebellar over extrapyramidal movement disorder predominance, and peripheral nervous system involvement. While this paper was in review, a highly resembling phenotype was reported in additional patients carrying the same c.2452 G>A variant. Our findings substantiate this variant as the cause of a unique inherited autosomal dominant neurologic syndrome that constitutes a third allelic disease of the ATP1A3 gene.

KEYWORDS:

CAPOS; alternating hemiplegia of childhood; deafness; intermittent weakness; rapid-onset dystonia parkinsonism

PMID:
25895915
DOI:
10.1177/0883073815579708
[Indexed for MEDLINE]

Supplemental Content

Full text links

Icon for Atypon
Loading ...
Support Center