Novel De Novo Mutations in KIF1A as a Cause of Hereditary Spastic Paraplegia With Progressive Central Nervous System Involvement.
J Child Neurol
; 31(9): 1114-9, 2016 08.
Article
en En
| MEDLINE
| ID: mdl-27034427
ABSTRACT
Hereditary spastic paraplegias are a clinically and genetically heterogeneous group of disorders characterized by lower extremity spasticity and weakness. Recently, the first de novo mutations in KIF1A were identified in patients with an early-onset severe form of complicated hereditary spastic paraplegia. We report two additional patients with novel de novo mutations in KIF1A, hereby expanding the genetic spectrum of KIF1A-related hereditary spastic paraplegia. Both children presented with spastic paraplegia and additional findings of optic nerve atrophy, structural brain abnormalities, peripheral neuropathy, cognitive/language impairment, and never achieved ambulation. In particular, we highlight the progressive nature of cerebellar involvement as captured on sequential magnetic resonance images (MRIs), thus linking the neurodegenerative and spastic paraplegia phenotypes. Exome sequencing in patient 1 and patient 2 identified novel heterozygous missense mutations in KIF1A at c.902G>A (p.R307Q) and c.595G>A (p.G199 R), respectively. Therefore, our report contributes to expanding the genotypic and phenotypic spectrum of hereditary spastic paraplegia caused by mutations in KIF1A.
Palabras clave
Texto completo:
1
Bases de datos:
MEDLINE
Asunto principal:
Paraplejía Espástica Hereditaria
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Cinesinas
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Predisposición Genética a la Enfermedad
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Mutación Missense
Tipo de estudio:
Prognostic_studies
Límite:
Adolescent
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Child
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Humans
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Male
Idioma:
En
Revista:
J Child Neurol
Asunto de la revista:
NEUROLOGIA
/
PEDIATRIA
Año:
2016
Tipo del documento:
Article
País de afiliación:
Estados Unidos