Exome sequencing identifies novel and recurrent mutations in GJA8 and CRYGD associated with inherited cataract.
Hum Genomics
; 8: 19, 2014 Nov 18.
Article
em En
| MEDLINE
| ID: mdl-25403472
ABSTRACT
BACKGROUND:
Inherited cataract is a clinically important and genetically heterogeneous cause of visual impairment. Typically, it presents at an early age with or without other ocular/systemic signs and lacks clear phenotype-genotype correlation rendering both clinical classification and molecular diagnosis challenging. Here we have utilized trio-based whole exome sequencing to discover mutations in candidate genes underlying autosomal dominant cataract segregating in three nuclear families.RESULTS:
In family A, we identified a recurrent heterozygous mutation in exon-2 of the gene encoding γD-crystallin (CRYGD; c.70C > A, p.Pro24Thr) that co-segregated with 'coralliform' lens opacities. Families B and C were found to harbor different novel variants in exon-2 of the gene coding for gap-junction protein α8 (GJA8; c.20T > C, p.Leu7Pro and c.293A > C, p.His98Pro). Each novel variant co-segregated with disease and was predicted in silico to have damaging effects on protein function.CONCLUSIONS:
Exome sequencing facilitates concurrent mutation-profiling of the burgeoning list of candidate genes for inherited cataract, and the results can provide enhanced clinical diagnosis and genetic counseling for affected families.
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Catarata
/
Conexinas
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Gama-Cristalinas
/
Exoma
Tipo de estudo:
Risk_factors_studies
Limite:
Female
/
Humans
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Male
Idioma:
En
Ano de publicação:
2014
Tipo de documento:
Article