Detecting genetic variations in hereditary retinal dystrophies with next-generation sequencing technology.
Mol Vis
; 20: 553-60, 2014.
Article
em En
| MEDLINE
| ID: mdl-24791140
ABSTRACT
PURPOSE:
To identify pathogenic mutations responsible for retinal dystrophies (RDs) in three unrelated Chinese families.METHODS:
Three probands from unrelated families with RDs were recruited. Genomic DNA prepared from leukocytes was analyzed using gene chip-based next-generation sequencing (NGS) to capture and sequence all of the exons of 100 known RD-associated genes. Candidate variants were validated with PCR and Sanger sequencing in the respective families. Thorough ophthalmic examinations including best-corrected visual acuity, funduscopic examination, and full-field electroretinograms were performed in the affected individuals.RESULTS:
We successfully identified causative mutations in patients from the Chinese families with RDS the known mutation IMPDH1 c.942_944delGAA in a family with retinitis pigmentosa, the novel mutation ABCA4 c.1924T>A in a family with Stargardt disease, and the novel mutation NMNAT1 c.272A>G and known mutation NMNAT1 c.196C>T in a family with Leber congenital amaurosis. All variations segregated with the disease phenotypes in the respective families and were absent from ethnically matched control chromosomes. Prediction analysis demonstrated the two novel missense mutations might be damaging.CONCLUSIONS:
The results strongly suggested these mutations were responsible for different RD phenotypes in the Chinese families. NGS technology provides an accurate and economic method for identifying causative genes for RDs.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Variação Genética
/
Predisposição Genética para Doença
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Distrofias Retinianas
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Sequenciamento de Nucleotídeos em Larga Escala
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Doenças Genéticas Inatas
Limite:
Child
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Female
/
Humans
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Male
/
Middle aged
Idioma:
En
Revista:
Mol Vis
Assunto da revista:
BIOLOGIA MOLECULAR
/
OFTALMOLOGIA
Ano de publicação:
2014
Tipo de documento:
Article
País de afiliação:
China