Assuntos
Adulto , Idade de Início , Hidrocarboneto de Aril Hidroxilases/genética , Sequência de Bases , Proteínas do Citoesqueleto/genética , Análise Mutacional de DNA , Proteínas do Olho/genética , Feminino , Glaucoma de Ângulo Aberto/enzimologia , Glicoproteínas/genética , Humanos , Índia/epidemiologia , Masculino , Dados de Sequência Molecular , Mutação/genéticaRESUMO
Glaucoma is the second largest blinding disorder, after cataract, affecting about 67 million people worldwide. In India about 1.5 million people are blind due to glaucoma. Primary open angle glaucoma is the major sub-type of glaucoma affecting all ages and is genetically complex. Myocilin and optineurin are two different genes that have been implicated for primary open angle glaucoma. This review is focused on the studies being conducted in India on primary open angle glaucoma to identify the molecular defects and new directions undertaken using bioinformatic approaches towards a better understanding of the disease.
Assuntos
Cegueira/etiologia , Cromossomos Humanos Par 10/genética , Biologia Computacional , Proteínas do Citoesqueleto/genética , Proteínas do Olho/genética , Glaucoma de Ângulo Aberto/classificação , Glicoproteínas/genética , Humanos , Índia , Fator de Transcrição TFIIIA/genética , Transtornos da Visão/etiologiaRESUMO
BACKGROUND & OBJECTIVES: Wilson disease (WD) is an autosomal recessive disorder caused by defects in ATP7B gene located in chromosome 13q14, and manifested as hepatolenticular degeneration as a result of accumulation of copper. No information on the mutation in the ATP7B gene and haplotypes using linked markers is available for WD patients in India. Hence, the present study was undertaken to identify, by a PCR-based molecular diagnostic test, presymptomatic siblings of WD affected individuals in families with multiple offspring. METHODS: Genomic DNA was prepared from the peripheral blood of the patients, siblings and his/her first degree relatives. The repeat-markers flanking WD locus were amplified by PCR using fluorescent labeled primers. Amplified DNA fragments were analyzed by polyacrylamide gel electrophoresis in ABI 377 DNA sequencing system. Genotypes of the samples were determined using Genescan software. Haplotypes were determined based on segregation of the alleles in the families under study. RESULTS: Among 15 WD affected families with multiple children, 4 cases were identified where younger siblings shared same genotype as the patient at all three markers analyzed. Further, eight different haplotypes were detected in the four patients. INTERPRETATION & CONCLUSION: The siblings of the WD patients carrying the same genotype at the markers linked to WD locus were presymptomatically diagnosed individuals. Presence of eight different haplotypes in the four patients suggested mutational heterogeneity at the WD locus. The test helps clinicians for therapeutic intervention in suspect WD cases by copper chelating agents prior to manifestation of overt clinical symptoms.