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Genetic analysis of families with autosomal recessive retinal dystrophies
Author(s) -
KANNABIRAN C,
SINGH H,
JALALI S
Publication year - 2008
Publication title -
acta ophthalmologica
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.534
H-Index - 87
eISSN - 1755-3768
pISSN - 1755-375X
DOI - 10.1111/j.1755-3768.2008.475.x
Subject(s) - candidate gene , genetics , disease gene identification , biology , abca4 , locus (genetics) , proband , gene , microsatellite , allele , phenotype , exome sequencing , mutation
Purpose To screen candidate gene loci in families with autosomal recessive RP Methods We used an approach of screening for homozygosity at candidate gene loci in affected individuals. 34 families with autosomal recessive RP (ARRP) or related phenotypes were included in the study of which 25 families were consanguineous, and all families had 2‐4 affected offspring. Patients and family members were clinically evaluated and blood samples were collected for DNA extraction after obtaining consent. Microsatellite markers flanking 23 known candidate genes for retinal dystrophy were genotyped in available members of all families. Microstallite markers selected were located in a 5.0 cM interval of the candidate gene. Families in which homozygosity was present and specific for all affected members at a candidate gene locus were further screened for mutations in the relevant gene. Coding regions of the genes were amplified using exon‐specific primers and subjected to direct sequencing. Results Screening of 23 gene loci revealed homozygosity shared by affected individuals in 10 out of 34 families. Homozygosity was detected at 2‐6 informative markers at each locus. The candidate gene loci are: ABCA4 (1p22.1), RPE65 (1p31), CRB1 (1q31), CNGA1 (4p12), PDE6B (4p16.3), TULP1 (6p21.3), RP1 (8q12.1), RGR (10q23), NRL (14q11) and RLBP1 (15q26). Putative pathogenic sequence changes were found in the probands upon screening the TULP1, ABCA4 and RPE65 genes. Screening of other candidate genes is in progress. Conclusion This approach enabled a rapid preliminary screen of known loci in recessive RP and may be suitable for identifying the disease locus in small consanguineous families.