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POLR3A-related spastic ataxia: new mutations and a look into the phenotype.

Abstract: Adolescent-onset spastic ataxia is a proposed novel phenotype in compound heterozygous carriers of an intronic mutation (c.1909?+?22G?>?A) in the POLR3A gene. Here, we present ten new cases of POLR3A-related spastic ataxia and discuss the genetic, clinical and imaging findings. Patients belonged to six pedigrees with hereditary spastic paraplegia or cerebellar ataxia of unknown origin. All affected subjects presented with compound heterozygous variants, comprising c.1909?+?22G?>?A in combination in each pedigree with one of the following novel mutations (Thr596Met, Tyr665LeufsTer11, Glu198Ter, c.646-687_1185?+?844del). The new mutations segregated with the phenotype in all families. The phenotype combined variable cerebellar ataxia, gait and lower limb spasticity, involvement of central sensory tracts and in some cases also intention tremor. The reportedly characteristic hyperintensity along the superior cerebellar peduncle on MRI was observed in?~?80% of the cases. Our study extends the clinical and molecular phenotype further supporting the pathogenic role of the c.1909?+?22G4A intronic mutation and identifying four novel causative mutations in POLR3A-related spastic ataxia. Certain characteristic MRI features may be useful to guide genetic diagnosis.

 Fuente: Journal of neurology 267, 324-330 (2020)

 Editorial: Springer

 Fecha de publicación: 01/02/2020

 Nº de páginas: 7

 Tipo de publicación: Artículo de Revista

 DOI: 10.1007/s00415-019-09574-9

 ISSN: 0340-5354,1432-1459

 Url de la publicación: https://doi.org/10.1007/s00415-019-09574-9

Autoría

SERRANO-CÁRDENAS, KARLA M.

CORRAL-JUAN, MARC

FARRÉ, XAVIER

SÁNCHEZ, IVELISSE

DE LUCAS, ENRIQUE M.

GARCÍA, ANTONIO

MARTÍN-GURPEGUI, JOSÉ LUIS

MATILLA-DUEÑAS, ANTONI