Confirmation of linkage and refinement of the RP28 locus forautosomal recessive retinitis pigmentosa on chromosome 2p14-p15 in anIndian family

[摘要] Purpose: To report the linkage analysis of retinitis pigmentosa (RP)in an Indian family.Methods: Individuals were examined for symptoms of retinitispigmentosa and their blood samples were withdrawn for genetic analysis.The disorder was tested for linkage to known 14 adRP and 22 arRP lociusing microsatellite markers.Results: Seventeen individuals including seven affectedsparticipated in the study. All affected individuals had typical RP. Theage of onset of the disease ranged from 8-18 years. The disorder in thisfamily segregated either as an autosomal recessive trait withpseudodominance or an autosomal dominant trait. Linkage to an autosomalrecessive locus RP28 on chromosome 2p14-p15 was positive with a maximumtwo-point lod score of 3.96 at theta=0 for D2S380. All affectedindividuals were homozygous for alleles at D2S2320, D2S2397, D2S380, andD2S136. Recombination events placed the minimum critical region (MCR)for the RP28 gene in a 1.06 cM region between D2S2225 and D2S296.Conclusions: The present data confirmed linkage of arRP to the RP28locus in a second Indian family. The RP28 locus was previously mapped toa 16 cM region between D2S1337 and D2S286 in a single Indian family.Haplotype analysis in this family has further narrowed the MCR for theRP28 locus to a 1.06 cM region between D2S2225 and D2S296. Of 15 genesreported in the MCR, 14 genes (KIAA0903, OTX1, MDH1,UGP2, VPS54, PELI1, HSPC159, FLJ20080, TRIP-Br2,SLC1A4, KIAA0582, RAB1A, ACTR2, and SPRED2) areeither expressed in the eye or retina. Further study needs to be done totest which of these genes is mutated in patients with RP linked to theRP28 locus.

[学科分类] 生物化学/生物物理