A novel locus (RP33) for autosomal dominant retinitis pigmentosa mapping to chromosomal region 2cen-q12.1.

Retinitis pigmentosa (RP) is a heterogeneous group of progressive degenerative disorders of the retina with a strong genetic component. Here, we report the clinical and genetic findings in a Chinese family in which autosomal dominant RP (adRP) was inherited by 13 affected members in four generations. Using a genome-wide linkage screening approach, a novel disease locus (RP33) was assigned to the long arm of chromosome 2. A maximum multi-point LOD score of 4.69 was reached at marker D2S2222 in 2q11.2. Meiotic recombination events in affected members placed RP33 in a 15.5 cM region between D2S329 and D2S2229. From meiotic recombinations in two unaffected members RP33 was further refined to a 4.8 cM (9.5 Mb) interval flanked by D2S2159 and D2S1343 in chromosomal region 2cen-q12.1. No disease-associated mutations were detected in the candidate genes SEMA4C, CNGA3 or HNK1ST from within the region. MERTK, a known disease gene for autosomal recessive RP located close to RP33 was similarly excluded. Clinically, the family presented relatively late onset of night blindness, gradually decreased visual acuity, progressive loss of peripheral visual field and typical RP fundus changes in the mid-periphery of the retina. In conclusion, a novel locus for adRP has been assigned to chromosomal region 2cen-q12.1, which in the present kindred was associated with a relatively late onset form of the disease.