An Ashkenazi Jewish founder mutation in CACNA1F causes retinal phenotype in both hemizygous males and heterozygous female carriers.
Ophthalmic Genet
; 40(5): 443-448, 2019 10.
Article
em En
| MEDLINE
| ID: mdl-31651202
ABSTRACT
Background:
Mutations in CACNA1F have been mainly associated with X-linked incomplete congenital stationary night blindness (icCSNB). Variable phenotypic expression in females was reported in some families. We report here three non-related Ashkenazi Jewish families originating in Eastern Europe, that included males and a many affected females, initially diagnosed with variable retinal phenotypes.Materials andMethods:
Whole exome sequencing (WES), Sanger sequencing and microsatellite haplotyping were used for genetic analysis. Complete ophthalmologic examination was performed including visual acuity, refraction, colour vision, slit-lamp, fundoscopy and electroretinography (ERG).Results:
We identified four affected males, showing moderate visual impairment, and seven female carriers, six of them presenting mild to moderate visual impairment. Infantile nystagmus was found in all affected males and in 5/7 females. Nyctalopia and myopia were common in both males and females. Initial clinical differential diagnosis included cone-dystrophy, cone-rod dystrophy, cone-dystrophy with supernormal rod response or CSNB based on ERG results. WES and Sanger sequencing revealed a previously described missense mutation c.2225T>G; p.(F742C) in CACNA1F (NM_001256789.2) in all three families, encompassed by a shared haplotypeConclusions:
Our data suggests that p.(F742C) in CACNA1F is an X-linked founder mutation in Ashkenazi Jews originating in Eastern Europe. This mutation causes a mild-to-moderate icCSNB phenotype, expressed in most female carriers. A targeted test for this variant in suspected patients may initiate diagnostic analysis. Our results highlight the relevance of WES in the clinic, allowing fast and accurate diagnosis for unclear and variable clinical phenotype and in pedigrees with multiple possible inheritance patterns.Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Policondrite Recidivante
/
Artrite
/
Doenças Retinianas
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Judeus
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Oftalmopatias Hereditárias
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Cegueira Noturna
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Mutação de Sentido Incorreto
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Canais de Cálcio Tipo L
/
Surdez
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Doenças Genéticas Ligadas ao Cromossomo X
Tipo de estudo:
Etiology_studies
/
Observational_studies
/
Prognostic_studies
/
Risk_factors_studies
Limite:
Adult
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Aged
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Female
/
Humans
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Male
/
Middle aged
Idioma:
En
Revista:
Ophthalmic Genet
Assunto da revista:
GENETICA MEDICA
/
OFTALMOLOGIA
Ano de publicação:
2019
Tipo de documento:
Article
País de afiliação:
Israel