Retinitis pigmentosa (RP) is the most frequent form of inherited retinopathy. RP is genetically heterogeneous with autosomal dominant, autosomal recessive and X-linked forms. Autosomal dominant retinitis pigmentosa (adRP) accounts for about 20-25% of all RP cases. At least ten adRP loci have so far been mapped. However, mutations causing adRP have been identified only in four retina-specific genes: RHO (encoding rhodopsin) in approximately 20% of adRP families, peripherin/RDS (3-5% of adRP) and recently RP1 (Pierce et al., 1999, Sulivan et al., 1999) and NRL gene. Only one mutation in the NRL gene causing adRP has so far been reported (Bessant et al., 1999). Here we report a novel mutation Pro51Leu in an adRP Spanish family supporting that mutation in NRL is the cause of adRP. A second missense mutation Gly122Glu has been observed in a simplex RP patient that may represent a sporadic case of retinitis pigmentosa. Hum Mutat 17:520, 2001.

Retinitis pigmentosa (RP) is a clinically and genetically heterogeneous group of retinal dystrophies, characterised by rod photoreceptor cell degeneration with autosomal recessive RP (arRP) as the commonest form worldwide. To date, a total of 26 loci have been reported for arRP, each having a prevalence of 1-5%, except for the RP25 locus which was identified as the genetic cause of 14% of arRP cases in Spain. In order to validate the original linkage of RP25, we undertook a total genome scan using the 10K GeneChip mapping array on three of the previously linked families. The data obtained supported the initial findings of linkage. Additionally, linkage analysis in 18 newly ascertained arRP families was performed using microsatellite markers spanning the chromosome 6p12.1-q15 interval. Five out of the 18 families showed suggestive evidence of linkage to RP25, hence supporting the high prevalence of this locus in the Spanish population. Furthermore, the finding of a crossover in one of these families is likely to have refined the disease interval from the original 16 cM to only a 2.67 cM region between D6S257 and D6S1557.

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