ATP8A2-related disorders as recessive cerebellar ataxia.
J Neurol
; 267(1): 203-213, 2020 Jan.
Article
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| MEDLINE
| ID: mdl-31612321
ABSTRACT
ATP8A2-related disorders are autosomal recessive conditions that associate encephalopathy with or without hypotonia, psychomotor delay, abnormal movements, chorea, tremor, optic atrophy and cerebellar atrophy (CARMQ4). Through a multi-centric collaboration, we identified six point mutations (one splice site and five missense mutations) involving ATP8A2 in six individuals from five families. Two patients from one family with the homozygous p.Gly585Val mutation had a milder presentation without encephalopathy. Expression and functional studies of the missense mutations demonstrated that protein levels of four of the five missense variants were very low and lacked phosphatidylserine-activated ATPase activity. One variant p.Ile215Leu, however, expressed at normal levels and displayed phospholipid-activated ATPase activity similar to the non-mutated protein. We therefore expand for the first time the phenotype related to ATP8A2 mutations to less severe forms characterized by cerebellar ataxia without encephalopathy and suggest that ATP8A2 should be analyzed for all cases of syndromic or non-syndromic recessive or sporadic ataxia.
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Base de datos:
MEDLINE
Asunto principal:
Ataxia Cerebelosa
/
Adenosina Trifosfatasas
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Proteínas de Transferencia de Fosfolípidos
Tipo de estudio:
Clinical_trials
Idioma:
En
Revista:
J Neurol
Año:
2020
Tipo del documento:
Article