BVVL/ FL: features caused by SLC52A3 mutations; WDFY4 and TNFSF13B may be novel causative genes.
Neurobiol Aging
; 99: 102.e1-102.e10, 2021 03.
Article
em En
| MEDLINE
| ID: mdl-33189404
ABSTRACT
Brown-Vialetto-Van Laere (BVVL) and Fazio-Londe are disorders with amyotrophic lateral sclerosis-like features, usually with recessive inheritance. We aimed to identify causative mutations in 10 probands. Neurological examinations, genetic analysis, audiometry, magnetic resonance imaging, biochemical and immunological testings, and/or muscle histopathology were performed. Mutations in known causative gene SLC52A3 were found in 7 probands. More importantly, only 1 mutated allele was observed in several patients, and variable expressivity and incomplete penetrance were clearly noted. Environmental insults may contribute to variable presentations. Putative causative mutations in other genes were identified in 3 probands. Two of the genes, WDFY4 and TNFSF13B, have immune-related functions. Inflammatory responses were implicated in the patient with the WDFY4 mutation. Malfunction of the immune system and mitochondrial anomalies were shown in the patient with the TNFSF13B mutation. Prevalence of heterozygous SLC52A3 BVVL causative mutations and notable variability in expressivity of homozygous and heterozygous genotypes are being reported for the first time. Identification of WDFY4 and TNFSF13B as candidate causative genes supports conjectures on involvement of the immune system in BVVL and amyotrophic lateral sclerosis.
Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Paralisia Bulbar Progressiva
/
Proteínas de Membrana Transportadoras
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Peptídeos e Proteínas de Sinalização Intracelular
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Fator Ativador de Células B
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Estudos de Associação Genética
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Mutação
Tipo de estudo:
Diagnostic_studies
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Prognostic_studies
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Risk_factors_studies
Limite:
Female
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Humans
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Male
Idioma:
En
Revista:
Neurobiol Aging
Ano de publicação:
2021
Tipo de documento:
Article
País de afiliação:
Irã