A Novel Genetic Study of Chinese Families with Autosomal Recessive Retinitis Pigmentosa

Abstract

SummaryAutosomal recessive retinitis pigmentosa (arRP) is the commonest form of RP worldwide. To date 22 loci have been implicated in the pathogenesis of this disease; however none of these loci independently account for a significant proportion of recessive RP. Linkage studies of arRP in consanguineous families have been mainly based on homozygosity mapping, but this strategy cannot be applied in the case of non-consanguineous families. Therefore, we implemented a systematic approach for identifying the disease locus in three non-consanguineous Chinese families with arRP. Initially, linkage analysis using SNPs/microsatellite markers or mutation screening of known arRP genes excluded all loci/genes except RP25 on chromosome 6. Subsequently a whole genome scan for the three families using the 10K GeneChip Mapping Array was performed, in order to identify the possible disease locus. To the best of our knowledge this is the first report on the utilisation of the 10K GeneChip to study linkage in non-consanguineous Chinese arRP. This analysis indicates that the studied families are probably linked to the RP25 locus, a well defined arRP locus in other populations. The identification of another ethnic group linked to RP25 is highly suggestive that this represents a major locus for arRP.

EYS is a major gene for rod-cone dystrophies in France

“…Until recently, most of the identified genes accounted for only 1-2% of cases each, besides USH2A (MIM# 608400) which was found to be mutated in more than 5% of arRP without hearing loss (Rivolta et al 2000;Bernal et al 2003). Linkage analysis, initially performed in Spanish families (Ruiz et al 1998), mapped the RP25 locus on chromosome 6q, which was subsequently reproduced in families from Pakistani (Khaliq et al 1999) and Chinese origins (Abd El-Aziz et al 2007). Additional Spanish families were also mapped to the same locus .…”

800 Facets of Retinal Degeneration

“…For example, in the same screen that identified Prominin, as well as in a behavioral screen for factors involved in the OPR-mediated optomotor response, a gene called spacemaker/eyes shut was isolated. [135][136][137][138] Given that 21 of the known 25 locus that result in arRP, excluding arRP25, account for only 30% of the arRP cases, these data indicate that arRP25 represents a significant portion of known arRP loci. [132][133][134] While arRP25 is characterized by the onset of night blindness and progressive degeneration of rods like other RPs, a uniquely identifying characteristic of arRP25 is that its prevalence represents up to 11% of all arRP cases, compared to the 1-5% seen with most arRPs.…”

Identification of a novel homozygous nonsense mutation in EYS in a Chinese family with autosomal recessive retinitis pigmentosa

“…Until recently, mutations of EYS have been detected in eight families [7,8]. Three Chinese families were linked to the RP25 locus, but no mutations were identified in the EYS gene [12]. Similarly, in one Pakistani arRP family, RP was suggested to be caused by an EYS mutation, too [10].…”

“…Then, the pathogenic genes for several arRP families with various ancestral origins, including one Pakistani family and three Chinese families, were also been mapped to this locus [10-12]. By using the 10K genechip array, Barragán I et al refined the disease interval from the original 16 cM to only a 2.67 cM region between D6S257 and D6S1557 [13].…”