Locus (RP30) for Severe Recessive Retinitis Pigmentosa Maps to Chromosome 1p13.3–p21.2 Between D1S2896 and D1S457 but Outside ABCA4

Abstract

Abstract: : Purpose: To describe clinical characteristics of a severe form of autosomal recessive retinitis pigmentosa (arRP) in a large Pakistani family and to map the disease locus. Methods: Family 61030 was ascertained in the Punjab province of Pakistan. Ocular examination included visual acuity, fundoscopy, and ERG. After exclusion of known arRP loci, a genome–wide scan was performed using microsatellite markers at about 10cM intervals and calculating two–point lod scores. PCR cycle dideoxynucleotide sequencing was used to sequence candidate genes inside the linked region for mutations. Results: All affected individuals in the family had nightblindness in early childhood, early complete loss of useful vision, and typical RP fundus changes plus macular degeneration. RP in this family showed linkage to markers in a 10.5cM (8.9Mb) region of chromosome 1p between D1S2896 and D1S457. D1S485 yields the highest lod score of 6.54 at theta = 0. Sequencing the exons and intron–exon boundaries of five candidate genes and six ESTs in this region, OLFM3, GNAI3, LOC126987, FLJ25070 DKFZp586G0123, AV729694, BU662869, BU656110, BU171991, BQ953690, and CA397743, did not identify any causative mutations. This new arRP locus is adjacent to ABCA4 but without overlap. Conclusions: A novel arRP locus (RP30) exists on 1p13.3–p21.2. This locus lies approximately 4.9cM (7.1Mb) from ABCA4, which is excluded from the linked region. Study of this gene may help to elucidate the phenotypic diversity of arRP mapping to this region.

Keywords: linkage analysis • retinal degenerations: hereditary • macula/fovea