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Alison J. Hardcastle, Dawn L. Thiselton, Ilaria Zito, Neil Ebenezer, Tammy S. Mah, Michael B. Gorin, Shomi S. Bhattacharya; Evidence for a New Locus for X-Linked Retinitis Pigmentosa (RP23). Invest. Ophthalmol. Vis. Sci. 2000;41(8):2080-2086.
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purpose. X-linked retinitis pigmentosa (XLRP) is a degenerative disease of the
retina characterized in the early stages of disease by night blindness
as a result of rod photoreceptor loss, progressing to severe disease
with loss of central vision by the third decade in affected males. XLRP
displays exceptional genetic heterogeneity, with five reported loci on
the human X-chromosome. To investigate the level of heterogeneity for
XLRP in the patient pool in the current study, extensive haplotype
analysis, linkage analysis, and mutation screening were performed.
methods. Haplotype analysis of a family with diagnosed XLRP was scored with more
than 34 polymorphic markers spanning the entire X-chromosome, including
regions already identified as harboring XLRP genes and retina-specific
genes. Two-point and multipoint lod scores were calculated. Affected
male DNA was amplified with primers specific for the retinoschisis gene
(XLRS1), and the products were screened for nucleic acid
alterations by direct automated sequencing.
results. In this article haplotype and linkage data are presented identifying a
new locus for XLRP on the short arm of the X-chromosome, distinct from
previously reported gene localizations for XLRP. The phenotype is
atypical, in that the onset of vision loss in the male members of this
family is unusually early, and female obligate carriers have normal
fundi and waveforms. Informative recombination events in this family
define a locus for XLRP (RP23) on Xp22 between the markers
DXS1223 and DXS7161, spanning approximately 15 cM. A maximum lod score
of 2.1 was calculated for the locus order DXS7103–8
cM–(RP23/DXS1224)–4 cM–DXS999. This new locus
(RP23) encompasses the retinoschisis disease gene;
therefore, XLRS1 was screened for a mutation. No sequence
alteration was identified indicating that mutations in the coding
region of the gene responsible for retinoschisis do not cause RP23.
conclusions. The results describe evidence for a new locus for XLRP
(RP23), adding to the established genetic heterogeneity for
this disease and the number of genes expressed in ocular tissue
residing on the X-chromosome.
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