RESUMO
BACKGROUND & OBJECTIVES: Bardet-Biedl syndrome (BBS) is a genetically heterogeneous autosomal recessive disorder characterized by multiple organ defects involving retina, kidney, liver and brain. Disease-causing mutations in BBS genes narrowed down by homozygosity mapping in small consanguineous and non-consanguineous pedigrees were reported in 80 per cent of the study population. This study was aimed to screen these genes (BBS3, BBS10) and specific exons of BBS genes (BBS1, BBS5, MKKS, BBS9, BBS11 and BBS12) for recurrent mutations in a selected sample of BBS patients. METHODS: The recurrent mutations in BBS genes were screened in the BBS affected individuals by PCR based direct sequencing. The pathogenicity of the observed mutations were confirmed by co-segregation analysis, screening of healthy unrelated controls and in silico analysis. RESULTS: In the 64 BBS patients (44 males, 20 females) were studied, mutations were predominant in BBS10 and ARL6 genes; the c.272T>C; p.(I91T) mutation in ARL6 gene was a recurrent mutation. One novel non-sense mutation c.425T>G; p(L142FNx01) was obtained in BBS5 gene (family BSI-31). INTERPRETATION & CONCLUSIONS: BBS10 gene mutations clustered in exon 2 of the gene suggesting the exon as a probable hotspot for mutations in Indian population. A cost- and time-effective strategy for the molecular diagnosis of BBS was designed based on these results.
Assuntos
Fatores de Ribosilação do ADP/genética , Síndrome de Bardet-Biedl/genética , Predisposição Genética para Doença , Chaperoninas do Grupo II/genética , Sequência de Aminoácidos , Síndrome de Bardet-Biedl/diagnóstico , Síndrome de Bardet-Biedl/patologia , Chaperoninas , Consanguinidade , Análise Mutacional de DNA , Éxons/genética , Feminino , Homozigoto , Humanos , Índia , Masculino , Mutação , Linhagem , Fenótipo , Polimorfismo de Nucleotídeo ÚnicoRESUMO
Gene mapping of inherited ophthalmic diseases such as congenital cataracts, retinal degeneration, glaucoma, age-related macular degeneration, myopia, optic atrophy, and eye malformations has shed more light on the disease pathology, identified targets for research on therapeutics, earlier detection, and treatment options for disease management and patient care. This article details the different approaches to gene identification for both Mendelian and complex eye disorders.
