Confirmation of linkage and refinement of the RP28 locus for autosomal recessive retinitis pigmentosa on chromosome 2p14-p15 in an Indian family.
OBJECTIVE
To report the linkage analysis of retinitis pigmentosa (RP) in an Indian family.


METHODS
Individuals were examined for symptoms of retinitis pigmentosa and their blood samples were withdrawn for genetic analysis. The disorder was tested for linkage to known 14 adRP and 22 arRP loci using microsatellite markers.


RESULTS
Seventeen individuals including seven affecteds participated in the study. All affected individuals had typical RP. The age of onset of the disease ranged from 8-18 years. The disorder in this family segregated either as an autosomal recessive trait with pseudodominance or an autosomal dominant trait. Linkage to an autosomal recessive locus RP28 on chromosome 2p14-p15 was positive with a maximum two-point lod score of 3.96 at theta=0 for D2S380. All affected individuals were homozygous for alleles at D2S2320, D2S2397, D2S380, and D2S136. 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 RP28 locus in a second Indian family. The RP28 locus was previously mapped to a 16 cM region between D2S1337 and D2S286 in a single Indian family. Haplotype analysis in this family has further narrowed the MCR for the RP28 locus to a 1.06 cM region between D2S2225 and D2S296. Of 15 genes reported in the MCR, 14 genes (KIAA0903, OTX1, MDH1, UGP2, VPS54, PELI1, HSPC159, FLJ20080, TRIP-Br2, SLC1A4, KIAA0582, RAB1A, ACTR2, and SPRED2) are either expressed in the eye or retina. Further study needs to be done to test which of these genes is mutated in patients with RP linked to the RP28 locus.
Kumar
Arun
A
Department of Molecular Reproduction, Development and Genetics, Indian Institute of Science, Bangalore, India. arunk00@hotmail.com
Shetty
Jyoti
J
Kumar
Bharath
B
Blanton
Susan Halloran
SH
D000293:Adolescent; D000328:Adult; D017668:Age of Onset; D002648:Child; D002874:Chromosome Mapping; D002889:Chromosomes, Human, Pair 2 / Q000235:genetics*; D003241:Consanguinity; D005260:Female; D005808:Genes, Recessive; D008040:Genetic Linkage; D005838:Genotype; D006801:Humans; D007194:India / Q000453:epidemiology; D008297:Male; D018895:Microsatellite Repeats; D008875:Middle Aged; D010375:Pedigree; D016133:Polymerase Chain Reaction; D012174:Retinitis Pigmentosa / Q000208:ethnology / Q000235:genetics*