The genetic profile of Leber congenital amaurosis in an Australian cohort.
Mol Genet Genomic Med
; 5(6): 652-667, 2017 11.
Article
em En
| MEDLINE
| ID: mdl-29178642
ABSTRACT
BACKGROUND:
Leber congenital amaurosis (LCA) is a severe visual impairment responsible for infantile blindness, representing ~5% of all inherited retinal dystrophies. LCA encompasses a group of heterogeneous disorders, with 24 genes currently implicated in pathogenesis. Such clinical and genetic heterogeneity poses great challenges for treatment, with personalized therapies anticipated to be the best treatment candidates. Unraveling the individual genetic etiology of disease is a prerequisite for personalized therapies, and could identify potential treatment candidates, inform patient management, and discriminate syndromic forms of disease.METHODS:
We have genetically analyzed 45 affected and 82 unaffected individuals from 34 unrelated LCA pedigrees using predominantly next-generation sequencing and Array CGH technology.RESULTS:
We present the molecular findings for an Australian LCA cohort, sourced from the Australian Inherited Retinal Disease Registry & DNA Bank. CEP290 and GUCY2D mutations, each represent 19% of unrelated LCA cases, followed by NMNAT1 (12%). Genetic subtypes were consistent with other reports, and were resolved in 90% of this cohort.CONCLUSION:
The high resolution rate achieved, equivalent to recent findings using whole exome/genome sequencing, reflects the progression from hypothesis (LCA Panel) to non-hypothesis (RD Panel) testing and, coupled with Array CGH analysis, is a highly effective first-tier test for LCA.Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Havaiano Nativo ou Outro Ilhéu do Pacífico
/
Amaurose Congênita de Leber
Tipo de estudo:
Diagnostic_studies
/
Etiology_studies
/
Incidence_studies
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Observational_studies
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Prevalence_studies
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Prognostic_studies
/
Risk_factors_studies
Limite:
Humans
País/Região como assunto:
Oceania
Idioma:
En
Revista:
Mol Genet Genomic Med
Ano de publicação:
2017
Tipo de documento:
Article