TY - JOUR
T1 - CAOS-Episodic Cerebellar Ataxia, Areflexia, Optic Atrophy, and Sensorineural Hearing Loss
AU - Heimer, Gali
AU - Sadaka, Yair
AU - Israelian, Lori
AU - Feiglin, Ariel
AU - Ruggieri, Alessandra
AU - Marshall, Christian R.
AU - Scherer, Stephen W.
AU - Ganelin-Cohen, Esther
AU - Marek-Yagel, Dina
AU - Tzadok, Michal
AU - Nissenkorn, Andreea
AU - Anikster, Yair
AU - Minassian, Berge A.
AU - Zeev, Bruria Ben
N1 - Publisher Copyright:
© The Author(s) 2015.
PY - 2015/11/1
Y1 - 2015/11/1
N2 - 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.
AB - 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.
KW - alternating hemiplegia of childhood
KW - CAPOS
KW - deafness
KW - intermittent weakness
KW - rapid-onset dystonia parkinsonism
UR - http://www.scopus.com/inward/record.url?scp=84944410503&partnerID=8YFLogxK
U2 - 10.1177/0883073815579708
DO - 10.1177/0883073815579708
M3 - Article
C2 - 25895915
AN - SCOPUS:84944410503
SN - 0883-0738
VL - 30
SP - 1749
EP - 1756
JO - Journal of Child Neurology
JF - Journal of Child Neurology
IS - 13
ER -