#601414
Table of Contents
A number sign (#) is used with this entry due to evidence that this form of retinitis pigmentosa, designated RP18, is caused by heterozygous mutation in the PRPF3 gene (607301) on chromosome 1q21.
For a phenotypic description and a discussion of genetic heterogeneity of retinitis pigmentosa, see 268000.
Xu et al. (1996) studied a large Danish family of 7 generations in which autosomal dominant retinitis pigmentosa segregated. Clinical diagnosis was based on a history of night blindness and ocular fundus findings typical of retinitis pigmentosa and included peripheral bone spicule formation, severe constriction of retinal arterioles, and progressive visual field defects beginning as midperipheral ring scotomas. Pathologic dark adaptation did not occur until the end of the first decade.
In a 7-generation Danish family with autosomal dominant retinitis pigmentosa, Xu et al. (1996) found linkage without recombination between RP18 and D1S498, which maps to chromosome 1q near the centromere. Analysis of multiple informative meioses suggests that in this family D1S534 and D1S305 flank RP18 in interval 1p13-q23. Xu et al. (1998) refined the genetic mapping of RP18 to a 2-cM region between D1S442 and D1S2858 on 1q.
Inglehearn et al. (1998) reported an English family with autosomal dominant retinitis pigmentosa mapping to this locus. Haplotype analysis placed the locus proximal to D1S1664. This marker is proximal to D1S2346, which is genetically indistinguishable from D1S2858; furthermore, 3 CEPH YACs containing D1S1664 did not contain either D1S2858 or D1S2346. Inglehearn et al. (1998) therefore concluded that their analysis further refined the distal boundary of the RP18 interval.
The transmission pattern of RP18 in the families reported by Chakarova et al. (2002) was consistent with autosomal dominant inheritance.
Chakarova et al. (2002) screened the PRPF3 gene, which they called HPRP3, in 3 chromosome 1q-linked autosomal dominant RP families. Two different missense mutations in 2 English families, a Danish family, and in 3 RP individuals were identified. One of the mutations (T494M; 607301.0001) was seen repeatedly in apparently unlinked families, raising the possibility of a mutation hotspot. Haplotype analysis with PRPF3 SNPs supported multiple origins for the mutation. The altered amino acids, which are highly conserved in all known PRPF3 orthologs, suggested a major function of that domain in the splicing process. Although PRPF3 appears to be ubiquitously expressed, the authors speculated that a retina-specific splicing element may interact with PRPF3 and generate the rod photoreceptor-specific phenotype.
Chakarova, C. F., Hims, M. M., Bolz, H., Abu-Safieh, L., Patel, R. J., Papaioannou, M. G., Inglehearn, C. F., Keen, T. J., Willis, C., Moore, A. T., Rosenberg, T., Webster, A. R., Bird, A. C., Gal, A., Hunt, D., Vithana, E. N., Bhattacharya, S. S. Mutations in HPRP3, a third member of pre-mRNA splicing factor genes, implicated in autosomal dominant retinitis pigmentosa. Hum. Molec. Genet. 11: 87-92, 2002. [PubMed: 11773002, related citations] [Full Text]
Inglehearn, C. F., Tarttelin, E. E., Keen, T. J., Bhattacharya, S., Moore, A. T., Taylor, R., Bird, A. C. A new dominant retinitis pigmentosa family mapping to the RP18 locus on chromosome 1q11-21. (Letter) J. Med. Genet. 35: 788-789, 1998. [PubMed: 9733043, related citations] [Full Text]
Xu, S., Rosenberg, T., Gal, A. Refined genetic mapping of autosomal dominant retinitis pigmentosa locus RP18 reduces the critical region to 2 cM between D1S442 and D1S2858 on chromosome 1q. Hum. Genet. 102: 493-494, 1998. [PubMed: 9600251, related citations] [Full Text]
Xu, S. Y., Schwartz, M., Rosenberg, T., Gal, A. A ninth locus (RP18) for the autosomal dominant retinitis pigmentosa maps in the pericentric region of chromosome 1. Hum. Molec. Genet. 5: 1193-1197, 1996. [PubMed: 8842740, related citations] [Full Text]
ORPHA: 791; DO: 0110356;
| Location | Phenotype |
Phenotype MIM number |
Inheritance |
Phenotype mapping key |
Gene/Locus |
Gene/Locus MIM number |
|---|---|---|---|---|---|---|
| 1q21.2 | Retinitis pigmentosa 18 | 601414 | Autosomal dominant | 3 | PRPF3 | 607301 |
A number sign (#) is used with this entry due to evidence that this form of retinitis pigmentosa, designated RP18, is caused by heterozygous mutation in the PRPF3 gene (607301) on chromosome 1q21.
For a phenotypic description and a discussion of genetic heterogeneity of retinitis pigmentosa, see 268000.
Xu et al. (1996) studied a large Danish family of 7 generations in which autosomal dominant retinitis pigmentosa segregated. Clinical diagnosis was based on a history of night blindness and ocular fundus findings typical of retinitis pigmentosa and included peripheral bone spicule formation, severe constriction of retinal arterioles, and progressive visual field defects beginning as midperipheral ring scotomas. Pathologic dark adaptation did not occur until the end of the first decade.
In a 7-generation Danish family with autosomal dominant retinitis pigmentosa, Xu et al. (1996) found linkage without recombination between RP18 and D1S498, which maps to chromosome 1q near the centromere. Analysis of multiple informative meioses suggests that in this family D1S534 and D1S305 flank RP18 in interval 1p13-q23. Xu et al. (1998) refined the genetic mapping of RP18 to a 2-cM region between D1S442 and D1S2858 on 1q.
Inglehearn et al. (1998) reported an English family with autosomal dominant retinitis pigmentosa mapping to this locus. Haplotype analysis placed the locus proximal to D1S1664. This marker is proximal to D1S2346, which is genetically indistinguishable from D1S2858; furthermore, 3 CEPH YACs containing D1S1664 did not contain either D1S2858 or D1S2346. Inglehearn et al. (1998) therefore concluded that their analysis further refined the distal boundary of the RP18 interval.
The transmission pattern of RP18 in the families reported by Chakarova et al. (2002) was consistent with autosomal dominant inheritance.
Chakarova et al. (2002) screened the PRPF3 gene, which they called HPRP3, in 3 chromosome 1q-linked autosomal dominant RP families. Two different missense mutations in 2 English families, a Danish family, and in 3 RP individuals were identified. One of the mutations (T494M; 607301.0001) was seen repeatedly in apparently unlinked families, raising the possibility of a mutation hotspot. Haplotype analysis with PRPF3 SNPs supported multiple origins for the mutation. The altered amino acids, which are highly conserved in all known PRPF3 orthologs, suggested a major function of that domain in the splicing process. Although PRPF3 appears to be ubiquitously expressed, the authors speculated that a retina-specific splicing element may interact with PRPF3 and generate the rod photoreceptor-specific phenotype.
Chakarova, C. F., Hims, M. M., Bolz, H., Abu-Safieh, L., Patel, R. J., Papaioannou, M. G., Inglehearn, C. F., Keen, T. J., Willis, C., Moore, A. T., Rosenberg, T., Webster, A. R., Bird, A. C., Gal, A., Hunt, D., Vithana, E. N., Bhattacharya, S. S. Mutations in HPRP3, a third member of pre-mRNA splicing factor genes, implicated in autosomal dominant retinitis pigmentosa. Hum. Molec. Genet. 11: 87-92, 2002. [PubMed: 11773002] [Full Text: https://doi.org/10.1093/hmg/11.1.87]
Inglehearn, C. F., Tarttelin, E. E., Keen, T. J., Bhattacharya, S., Moore, A. T., Taylor, R., Bird, A. C. A new dominant retinitis pigmentosa family mapping to the RP18 locus on chromosome 1q11-21. (Letter) J. Med. Genet. 35: 788-789, 1998. [PubMed: 9733043] [Full Text: https://doi.org/10.1136/jmg.35.9.788]
Xu, S., Rosenberg, T., Gal, A. Refined genetic mapping of autosomal dominant retinitis pigmentosa locus RP18 reduces the critical region to 2 cM between D1S442 and D1S2858 on chromosome 1q. Hum. Genet. 102: 493-494, 1998. [PubMed: 9600251] [Full Text: https://doi.org/10.1007/s004390050728]
Xu, S. Y., Schwartz, M., Rosenberg, T., Gal, A. A ninth locus (RP18) for the autosomal dominant retinitis pigmentosa maps in the pericentric region of chromosome 1. Hum. Molec. Genet. 5: 1193-1197, 1996. [PubMed: 8842740] [Full Text: https://doi.org/10.1093/hmg/5.8.1193]
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