Homozygosity Mapping in Leber Congenital Amaurosis and Autosomal Recessive Retinitis Pigmentosa in South Indian Families
| Autor: | Vetrivel Umashankar, Natarajan N. Srikrupa, Suman Kapur, Parveen Sen, Tharigopala Arokiasamy, Nagasamy Soumittra, Swaminathan Meenakshi, Sundaramurthy Srilekha |
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| Jazyk: | angličtina |
| Rok vydání: | 2015 |
| Předmět: |
Male
Candidate gene Genotype genetic structures DNA Mutational Analysis Leber Congenital Amaurosis India lcsh:Medicine Locus (genetics) Consanguinity Biology Polymorphism Single Nucleotide Retina Autosomal recessive trait Proto-Oncogene Proteins Retinitis pigmentosa medicine Humans Eye Proteins lcsh:Science Oligonucleotide Array Sequence Analysis Genetics Multidisciplinary CRB1 c-Mer Tyrosine Kinase Homozygote Retinal Degeneration lcsh:R Receptor Protein-Tyrosine Kinases medicine.disease Disease gene identification eye diseases Pedigree Phenotype Mutation GUCY2D Female lcsh:Q sense organs Retinitis Pigmentosa Research Article |
| Zdroj: | PLoS ONE, Vol 10, Iss 7, p e0131679 (2015) PLoS ONE |
| ISSN: | 1932-6203 |
| Popis: | Leber congenital amaurosis (LCA) and retinitis pigmentosa (RP) are retinal degenerative diseases which cause severe retinal dystrophy affecting the photoreceptors. LCA is predominantly inherited as an autosomal recessive trait and contributes to 5% of all retinal dystrophies; whereas RP is inherited by all the Mendelian pattern of inheritance and both are leading causes of visual impairment in children and young adults. Homozygosity mapping is an efficient strategy for mapping both known and novel disease loci in recessive conditions, especially in a consanguineous mating, exploiting the fact that the regions adjacent to the disease locus will also be homozygous by descent in such inbred children. Here we have studied eleven consanguineous LCA and one autosomal recessive RP (arRP) south Indian families to know the prevalence of mutations in known genes and also to know the involvement of novel loci, if any. Complete ophthalmic examination was done for all the affected individuals including electroretinogram, fundus photograph, fundus autofluorescence, and optical coherence tomography. Homozygosity mapping using Affymetrix 250K HMA GeneChip on eleven LCA families followed by screening of candidate gene(s) in the homozygous block identified mutations in ten families; AIPL1 – 3 families, RPE65- 2 families, GUCY2D, CRB1, RDH12, IQCB1 and SPATA7 in one family each, respectively. Six of the ten (60%) mutations identified are novel. Homozygosity mapping using Affymetrix 10K HMA GeneChip on the arRP family identified a novel nonsense mutation in MERTK. The mutations segregated within the family and was absent in 200 control chromosomes screened. In one of the eleven LCA families, the causative gene/mutation was not identified but many homozygous blocks were noted indicating that a possible novel locus/gene might be involved. The genotype and phenotype features, especially the fundus changes for AIPL1, RPE65, CRB1, RDH12 genes were as reported earlier. |
| Databáze: | OpenAIRE |
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