title: Homozygosity Mapping in Leber Congenital Amaurosis and Autosomal Recessive Retinitis Pigmentosa in South Indian Families.
abstract: 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.
authors.affiliation: SNONGC Department of Genetics and Molecular Biology, Vision Research Foundation, Chennai, India; Ph.D Scholar, Birla Institute of Technology & Science (BITS), Hyderabad, India.
authors.forename: Sundaramurthy
authors.initials: S
authors.lastname: Srilekha
authors.affiliation: SNONGC Department of Genetics and Molecular Biology, Vision Research Foundation, Chennai, India.
authors.forename: Tharigopala
authors.initials: T
authors.lastname: Arokiasamy
authors.affiliation: SNONGC Department of Genetics and Molecular Biology, Vision Research Foundation, Chennai, India; Ph.D Scholar, Birla Institute of Technology & Science (BITS), Hyderabad, India.
authors.forename: Natarajan N
authors.initials: NN
authors.lastname: Srikrupa
authors.affiliation: Head, Centre for Bioinformatics, Vision Research Foundation, Chennai, India.
authors.forename: Vetrivel
authors.initials: V
authors.lastname: Umashankar
authors.affiliation: Department of Peadiatric ophthalmology and starbismus, Medical Research Foundation, Chennai, India.
authors.forename: Swaminathan
authors.initials: S
authors.lastname: Meenakshi
authors.affiliation: Department of Vitreo-Retinal Services, Medical Research Foundation, Chennai, India.
authors.forename: Parveen
authors.initials: P
authors.lastname: Sen
authors.affiliation: Head, Department of Biological Science, Birla Institute of Technology & Science (BITS), Hyderabad, India.
authors.forename: Suman
authors.initials: S
authors.lastname: Kapur
authors.affiliation: SNONGC Department of Genetics and Molecular Biology, Vision Research Foundation, Chennai, India.
authors.forename: Nagasamy
authors.initials: N
authors.lastname: Soumittra
mesh_terms: D003241:Consanguinity; D004252:DNA Mutational Analysis / Q000379:methods; D005136:Eye Proteins / Q000235:genetics; D005260:Female; D005838:Genotype; D006720:Homozygote; D006801:Humans; D007194:India; D057130:Leber Congenital Amaurosis / Q000235:genetics*; D008297:Male; D009154:Mutation / Q000235:genetics; D020411:Oligonucleotide Array Sequence Analysis / Q000379:methods; D010375:Pedigree; D010641:Phenotype; D020641:Polymorphism, Single Nucleotide / Q000235:genetics; D011518:Proto-Oncogene Proteins / Q000235:genetics; D020794:Receptor Protein-Tyrosine Kinases / Q000235:genetics; D012160:Retina / Q000473:pathology; D012162:Retinal Degeneration / Q000235:genetics; D012174:Retinitis Pigmentosa / Q000235:genetics*; D000076202:c-Mer Tyrosine Kinase
chemical_list: D005136:Eye Proteins; D011518:Proto-Oncogene Proteins; C097072:MERTK protein, human; D020794:Receptor Protein-Tyrosine Kinases; D000076202:c-Mer Tyrosine Kinase