Showing papers in "Ophthalmic Genetics in 2001"

Update on the molecular genetics of retinitis pigmentosa.

Abstract: Retinitis pigmentosa (RP) is a heterogeneous group of retinal dystrophies characterized by photoreceptor cell degeneration. RP causes night blindness, a gradual loss of peripheral visual fields, and eventual loss of central vision. Advances in molecular genetics have provided new insights into the genes responsible and the pathogenic mechanisms of RP. The genetics of RP is complex, and the disease can be inherited in autosomal dominant, recessive, X-linked, or digenic modes. Twenty-six causative genes have been identified or cloned for RP, and an additional fourteen genes have been mapped, but not yet identified. Eight autosomal dominant forms are due to mutations in RHO on chromosome 3q21-24, RDS on 6p21.1-cen, RP1 on 8p11-21, RGR on 10q23, ROM1 on 11q13, NRL on 14q11.1-11.2, CRX on 19q13.3, and PRKCG on 19q13.4. Autosomal recessive genes include RPE65 on chromosome 1p31, ABCA4 on 1p21-13, CRB1 on 1q31-32.1, USH2A on 1q41, MERTK on 2q14.1, SAG on 2q37.1, RHO on 3q21-24, PDE6B on 4p16.3, CNGA1 on 4p14-q13, PDE6A on 5q31.2-34, TULP1 on 6p21.3, RGR on 10q, NR2E3 on 15q23, and RLBP1 on 15q26. For X-linked RP, two genes, RP2 and RP3 (RPGR), have been cloned. Moreover, heterozygous mutations in ROM1 on 11q13, in combination with heterozygous mutations in RDS on 6p21.1-cen, cause digenic RP (the two-locus mechanism). These exciting molecular discoveries have defined the genetic pathways underlying the pathogenesis of retinitis pigmentosa, and have raised the hope of genetic testing for RP and the development of new avenues for therapy.

Osteosarcoma following retinoblastoma: age at onset and latency period

Abstract: In order to assess the role of genetic predisposition in the induction of radiation-induced tumors, we performed statistical analysis on data from the literature and from our own Institute with regard to the age at onset and the latency period of osteosarcoma as the second primary tumor for retinoblastoma with or without subsequent radiotherapy. In retinoblastoma survivors who subsequently developed osteosarcoma, the age at onset of retinoblastoma was young (average of 12 months) in both unilateral and bilateral forms. This suggests that all or almost all of the patients were genetically predisposed by a mutation of one allele of the RB1 gene. For retinoblastoma patients, osteosarcomas occurred 1.2 years earlier inside than outside the radiation field. The latency period between radiotherapy and osteosarcoma onset was 1.3 years shorter inside than outside the radiation field. Interestingly, a bimodal distribution of latency periods was observed for osteosarcomas arising inside, but not outside the radiation field: 40% occurred after a short latency, while the latency of the remaining 60% was comparable to that of osteosarcoma occurring outside the radiation field. This suggests that different mechanisms may be involved in radiocarcinogenesis. A radiation-induced mutation of the second RB1 allele may be the cause of osteosarcomas occurring after a short delay, while other genes may be affected in those occurring after a longer delay.

CRB1 mutations may result in retinitis pigmentosa without para-arteriolar RPE preservation

Abstract: Purpose: To report a new phenotype in retinitis pigmenotosa (RP) patients with CRB1 mutations at the RP12 locus. Patients: Thirty-seven patients from two Pakistani families with severe retinitis pigmentosa. Methods: Samples were screened with single-strand conformation polymorphism analysis followed by DNA sequencing of the coding sequence of the CRB1 gene. Results: Two novel CRB1 mutations were discovered. No patients had evidence of preservation of the para-arteriolar retinal pigment epithelium (PPRPE) that has been previously reported in all cases of RP associated with CRB1 mutations. Conclusions: Patients with severe autosomal recessive (or simplex) RP who lack the finding of PPRPE should not be excluded from molecular analysis of CRB1 purely because they lack the clinical feature of PPRPE. This report illustrates that RP at the RP12 locus is not clinically uniform. The absence of PPRPE cannot be used to exclude CRB1 as a potential molecular explanation for RP.

Evaluation of the ELOVL4 gene in patients with age-related macular degeneration.

Abstract: Stargardt-like macular degeneration (STGD3) and autosomal dominant macular degeneration (adMD) share phenotypic characters with atrophic age-related macular degeneration (AMD). Mutations in a photoreceptor cell-specific factor involved in the elongation of very long chain fatty acids ( ELOVL4 ) were shown to be associated with STGD3, adMD, and pattern dystrophy. We screened 778 patients with AMD and 551 age-matched controls to define the role of sequence variants in the ELOVL4 gene in age-related macular degeneration. We detected three sequence variants in the non-coding region and eight variants in the coding region. No statistically significant association was observed between sequence variants in the ELOVL4 gene and susceptibility to AMD. However, for the detection of modest effects of multiple alleles in a complex disease, the analysis of larger cohorts of patients may be required.

Further refinement of the MYP2 locus for autosomal dominant high myopia by linkage disequilibrium analysis.

Abstract: Introduction: High myopia (>-6.00 diopters) is a complex common disorder that predisposes individuals to retinal detachment, glaucoma, macular degeneration, and premature cataracts. A recent linkage analysis of seven families with autosomal dominant high myopia has identified one locus (MYP2) for high myopia on chromosome 18p11.31 (Young et al.: Am J Hum Genet 1998;63:109–119). Haplotype analysis revealed an initial interval of 7.6 centimorgans (cM). Methods: Transmission disequilibrium tests (TDT) with both the Statistical Analysis for Genetic Epidemiology (SAGE) 3.1 TDTEX and GENEHUNTER 2 (GH2) programs were performed using chromosome 18p marker alleles for this interval. Results: Using SAGE analysis, the following p values were obtained for markers in marker order in this region: D18S1146 (p = 0.227), D18S481 (p = 0.001), D18S63 (p = 0.062), D18S1138 (p = 0.0004), D18S52 (p = 1.79 × 10 -6 ), and D18S62 (p = 0.141). GH2 TDT analysis revealed the following p values for the best allele for the markers:...

Exfoliation syndrome: Clinical and genetic features

Abstract: We have ascertained a large number of individuals and families with exfoliation syndrome in order to clarify the disorder’s mode of inheritance. Patients with exfoliation syndrome and their relatives were recruited from the practices of a group of ophthalmologists in Maritime Canada. The degree to which the subjects were affected was graded according to a standardized 1–4-point clinical scheme. Pedigrees were constructed from information supplied by family members and from genealogical sources. A total of 782 patients and relatives participated, of whom 467 were definitely affected. The mean age of affected males and females did not differ significantly, but females appeared to be more severely affected at ascertainment than males. More than half of the affected subjects had definite exfoliation in only one eye. Approximately 30 multiplex families were discovered, including one containing 23 affected members among a total of 137 examined individuals that constitutes the largest exfoliative pedigree thus f...

Neuronal cell death in the visual cortex is a prominent feature of the X-linked recessive mitochondrial deafness-dystonia syndrome caused by mutations in the TIMM8a gene.

Abstract: The Mohr-Tranebjaerg syndrome (MIM 304700) and the Jensen syndrome (MIM 311150) were previously reported as separate X-linked recessive deafness syndromes associated with progressive visual deterioration, dystonia, dementia, and psychiatric abnormalities. In the most extensively studied Norwegian family, the Mohr-Tranebjaerg syndrome was reported to be caused by a one-basepair deletion (151delT) in the deafness/dystonia peptide ( DDP ) gene at Xq22. This gene has been renamed TIMM8a . We identified a stop mutation (E24X) in the TIMM8a gene segregating with the disease in the original Danish family with the Jensen syndrome, which confirms that the two disorders are allelic conditions. We also report abnormal VEP examinations and neuropathological abnormalities in affected males from the two unrelated families with different mutations. The findings included neuronal cell loss in the optic nerve, retina, striate cortex, basal ganglia, and dorsal roots of the spinal cord. The demonstration of mitochondrial abno...

Clinical and genetic analysis of a family with X-linked congenital nystagmus (NYS1)

Abstract: Purpose: To describe a family with X-linked congenital nystagmus and identify the genetic interval within which the gene is located. Methods and design: Clinical examination with genotyping of 30 individuals from a multi-generational Caucasian family with congenital nystagmus inherited in an X-linked pattern using markers from Xq26–q27, followed by linkage analysis and sequencing of a candidate gene, solute carrier family 25, member 14 (SLC25A14), in four affected individuals from four families linked to this region. Results: The pattern of inheritance in the family was consistent with X-linkage with incomplete penetrance among carrier females. No affected males had affected sons. Based on the extended pedigree, the estimated penetrance among obligate female carriers (daughters of affected males) was 29% (6 of 21). Visual acuity among 15 affected individuals ranged from 20/20 to 20/70 (median 20/30). Clinical examinations, includ-ing electroretinography in two individuals, were otherwise normal except for...

Best’s vitelliform macular dystrophy caused by a new mutation (Val89Ala) in the VMD2 gene

Abstract: Purpose: To describe the clinical phenotype in a family with Best’s vitelliform macular dystrophy (BMD) and a new mutation (Val89Ala) in the VMD2 gene. Methods: The genotype was determined by direct sequence analysis of the individual exons of VMD2. Nine members of a family with BMD were examined. The examination included best-corrected visual acuity, electro-oculography (EOG), fundus examination, and photography. Four of the patients were also examined with full-field ERG and three with multifocal ERG. Results: A T-to-C substitution was identified at position 370 in the cDNA of VMD2, leading to a Val89Ala change in the protein. Six patients, five with the Val89Ala mutation and a nine-year-old boy without the mutation, presented with a pathological Arden ratio on EOG examination. Most of the patients with BMD in this family had an onset of visual failure by the age of 40–50 years. The older patients in the family demonstrated atrophic macular dystrophy. Conclusions: Patients with BMD and the Val89Ala muta...

Electrophysiologic findings in two young patients with Bothnia dystrophy and a mutation in the RLBP1 gene

Abstract: Purpose: To characterize the clinical phenotype, with emphasis on electrophysiology, of two children with suspected Bothnia dystrophy. Methods: Two unrelated affected patients, 10 and 11 years old, were studied. Ophthalmological examination included testing of visual acuity, fundus inspection and fundus photography, kinetic perimetry, full-field electroretinogram (ERG), and multifocal ERG. The presence of a mutation in exon 7 of the RLBP1 gene was investigated by DNA sequencing. Results: Both patients were homozygous for the Arg234Trp-causing mutation in the RLBP1 gene, but the resulting disease phenotype appeared to vary somewhat between them. Visual acuity was moderately reduced in one patient and normal in the other. Fundus inspection at this age revealed no pathology in either patient and there were no signs of retinitis punctata albescens, which has been described previously as a frequent clinical feature of Bothnia dystrophy. The result of kinetic perimetry was normal. The final rod threshold was moderately elevated. Full-field ERG demonstrated the uncommon combination of absent rod response and normal cone response after 40 minutes of dark adaptation. However, after prolonged dark adaptation (20-24 h), both the rod response and the dark adaptation threshold became normal. Multifocal ERG was performed in one of the patients (the one with normal visual acuity and normal fundus appearance) and showed a reduced cone response in the central region of the tested area. There was no improvement of the multifocal ERG result after 20-24 h of dark adaptation. Conclusion: Patients with mutations in the RLBP1 gene (Arg234Trp) may have a normal fundus appearance early in the disease course. Multifocal ERG can be used for the objective documentation of the disturbed macular function, especially when the patient's visual acuity and fundus appearance are normal. The rod response is absent in the electroretinogram; however, after prolonged dark adaptation (20-24 hours), the rods recover completely. The central cones do not seem to recover. (Less)

Non-visual ocular photoreception.

Abstract: At least six light-regulated phenomena are preserved in the eyes of retinally degenerate mice, including the entrainment of circadian rhythms, the gating of ocular immune response, and pupillary reactivity. Some of these phenomena have also been observed in blind human patients. These findings have prompted the search for a non-visual ocular phototransduction mechanism. Molecular genetic studies have identified several candidate genes for these effects. These include genes encoding novel ocular opsins, such as melanopsin, as well as potential flavin-based photopigments. Data linking these potential photoreceptors to these phenomena are discussed, and the clinical implications of these findings are explored.

Further delineation of the facial 13q14 deletion syndrome in 13 retinoblastoma patients.

Abstract: Thirteen years ago, Motegi and colleagues (J Med Genet 1987;24:696–697) summarized the specific facial phenotype of six Japanese retinoblastoma patients with interstitial 13q14 deletions. Among a series of 228 propositi with retinoblastoma referred to the Lausanne Retinoblastoma Clinic for treatment and genetic counseling between 1986 and 1997, 13 (5.7%) were diagnosed with a cytogenetic de-novo 13q14 deletion. We confirm the presence of the reported facial phenotype in our population of Caucasian patients and describe additional clinical traits, thus extending the facial phenotype associated with the 13q14 deletion. Del(13q14) comprises, among others, cranial anomalies, frontal bossing, deeply grooved and long philtrum, depressed and broad nasal bridge, bulbous tip of the nose, thick lower lip, thin upper lip, broad cheeks, and large ears and lobules. Recognition of this particular facial appearance was instrumental in the genetic diagnosis of 13q deletions and in the presymptomatic diagnosis of retinobl...

Screening for CRX gene mutations in Chinese patients with Leber congenital amaurosis and mutational phenotype.

Abstract: Purpose: To screen for possible disease-causing mutations in the CRX gene in Chinese patients with Leber congenital amaurosis (LCA) and to enrich the understanding of its mutational phenotype. Methods: Genomic DNA was collected from 27 patients with LCA. The coding sequences of the CRX gene were analyzed using the PCR-heteroduplex-SSCP method. Mutations were confirmed by DNA sequencing. Results: We identified two heterozygous variations in the CRX gene in two patients with LCA. One was a deletion (GCC?-CC, A181?1bp) leading to a frameshift and protein truncation. This mutation was present in a patient with LCA, but not in his healthy parents. The ocular manifestations of this A181?1bp mutation are described. An intronic variation (IVS1-13G?C) was found in a patient with LCA as well as in his healthy father. Conclusion: A heterozygous A181?1bp mutation in the CRX gene caused an LCA phenotype in a Chinese patient.

Association of retinopathy with a microsatellite at 5' end of the aldose reductase gene in Chinese patients with late-onset Type 2 diabetes.

Abstract: Recent experimental data suggest that a microsatellite polymorphism at 5' end of the aldose reductase gene may be associated with the development of diabetic retinopathy. In the present study, we examined the allele distribution of the polymorphism in 384 Hong Kong Chinese patients who had late-onset (age at diagnosis =35 years) Type 2 diabetes, but no clinical evidence of cataract. Approximately 17% of them (n = 64) had retinopathy. The patients with retinopathy were older (52 ± 11 years vs. 60 ± 9 years, p < 0.01) and had a higher HbA 1c (8.9 ± 2.2% vs. 7.7 ± 2.0%, p < 0.01 with adjustment for age) than those without the complication. Amongst all of the patients, we detected 10 microsatellite alleles and found that allele Z-4 was overpresented in those with retinopathy (9% vs. 4%, p < 0.05). There were no significant differences in allelic distributions of the major alleles Z + 2, Z, and Z-2, which accounted for more than 80% of the overall frequency, between the two groups of patients. Using m...

MYOC mutation frequency in primary open-angle glaucoma patients from Western Switzerland.

Abstract: Purpose: To determine MYOC gene mutation frequency in patients with primary open-angle glaucoma (POAG) from Western Switzerland. Methods: A total of 117 unselected index patients with primary open-angle glaucoma were submitted to a full eye examination. DNA was extracted from blood and PCR amplicons of MYOC exon 3 were screened for mutations by single-strand conformation polymorphism (SSCP) analysis. Abnormal conformers were analyzed both by direct bidirectional sequencing and by enzymatic mutation detection (EMD) assay. Results: Ten occurrences of four different sequence changes were detected, including: 1) five times the same disease-causing mutation (Q368X) in five unrelated POAG patients and 2) three distinct polymorphisms in five patients. The patients carrying an MYOC mutant allele were characterized by a broad clinical variability in terms of age of onset (34–77 years) and highest intraocular pressure (IOP) values (23–47 mmHg). Conclusions: A pathogenic MYOC mutation (Q368X) was identified in 4.27%...

Molecular and clinical characterization of a patient with a chromosome 4p deletion, Wolf-Hirschhorn syndrome, and congenital glaucoma.

Abstract: Wolf-Hirschhorn syndrome is a developmental disorder associated with hemizygous deletion of the distal short arm of chromosome 4. We have identified a patient affected with Wolf-Hirschhorn syndrome and early onset glaucoma. Five other patients with Wolf-Hirschhorn syndrome and early onset glaucoma or ocular anomalies associated with early onset glaucoma have been previously described, suggesting that the association with Wolf-Hirschhorn syndrome is not coincidental. The infrequent association of early onset glaucoma suggests that the chromosomal region commonly deleted in Wolf-Hirschhorn patients does not contain genes responsible for early onset glaucoma. In this study, we performed a molecular characterization of the deleted chromosome 4 to determine the extent of the deletion in an attempt to begin to identify the chromosomal region responsible for the associated glaucoma. Using microsatellite repeat markers located on 4p, we determined that the deletion spanned a 60-cM region including the minimal Wol...

Peripapillary staphyloma associated with orofacial capillary hemangioma.

Abstract: Peripapillary staphyloma is usually unassociated with other ocular and systemic anomalies. A 5-year-old girl presented with peripapillary staphyloma in association with extensive ipsilateral orofacial capillary hemangioma involving the right forehead, right upper and lower eyelids, the right cheek, and the hard palate. She had received oral corticosteroids to induce regression of the hemangiomas at six months of age. On our examination, her visual acuity was counting fingers at two meters right eye and 20/20 left eye. She had mild right upper eyelid ptosis and right exotropia. Imaging studies did not show any central nervous system abnormality. There has been no progression or contraction in the staphylomatous lesion during 24 months of follow-up. Like the morning glory disk anomaly, peripapillary staphyloma may be associated with facial capillary hemangioma.

Laboratory methods in ophthalmic genetics: obtaining DNA from patients

Abstract: DNA samples are the fundamental research substrate in genetics. Although methodology and cost-effectiveness in molecular biology have improved dramatically, collecting biological samples and extracting DNA continue to be expensive and time-consuming steps of genetic research. This article reviews the issues surrounding the choice of biological samples for methods of DNA extraction as well as the storage and transport of biological and DNA samples for genetic studies.

Novel deletion of the RPGR gene in a Chinese family with X-linked retinitis pigmentosa.

Abstract: Purpose: To characterize a Chinese family with inherited retinitis pigmentosa (RP). Methods: Linkage studies and haplotype analysis were used for gene mapping, and single-strand conformation polymorphism (SSCP) analysis and direct DNA sequence analysis were used for identifying the responsible mutation. Results: Pedigree analysis suggests that RP in the Chinese family RP002 is inherited either as an autosomal recessive trait or as an X-linked trait. Linkage analysis of RP002 excluded all known autosomal recessive RP loci. Further analysis with 17 polymorphic markers covering the entire X chromosome localized the RP gene in RP002 between markers GATA175D03 and GATA144D04 on Xp11.4, a region where the RP3 gene ( RPGR ) is found. Mutation analysis of the RPGR gene in RP002 revealed a novel 28-bp deletion in exon 7. This deletion resulted in an in-frame stop codon that eliminates the C-terminal two-thirds of the RPGR protein. The 28-bp deletion co-segregated with the disease in the family and was not present ...

Novel rhodopsin mutation in a Chinese family with autosomal dominant retinitis pigmentosa.

Abstract: Purpose: To identify mutations in the rhodopsin ( RHO ) gene in Chinese patients with autosomal dominant retinitis pigmentosa (ADRP) and to measure the prevalence rate of RHO mutations in Chinese ADRP cases. Methods: Thirteen Chinese families with ADRP were clinically characterized. The complete coding region and intron splice sites of RHO were analyzed for mutations with single-strand conformation polymorphism (SSCP) analysis and direct genomic sequencing. Results: One of the 13 Chinese families with ADRP was found to have a new, previously unidentified RHO mutation, a change from GAG to TAG at codon 341. The mutation (E341X) results in an in-frame stop codon, leading to the truncation of the rhodopsin protein. Mutation E341X was not detected in 100 normal control individuals. Patients carrying mutation E341X reported night blindness and showed optic atrophy, vessel attenuation, and a few bone spicule-like pigments in peripheral retina at the age of 23–25 years. At the age of 30 years, visual acuity was ...

An infant with Down syndrome and retinoblastoma. A possible non-fortuitous association.

Abstract: Aim: To evaluate the association between Down syndrome and retinoblastoma Method: Presentation of a case report and review of the literature Results: A retinoblastoma was observed in a 10-month-old boy with Down syndrome A review of the literature yielded 14 other cases, suggesting a possible excess of retinoblastoma in Down syndrome, as previously proposed by two epidemiological studies The possible roles of external physical agents and hyperplastic and dysplastic lesions of the retina in subjects with Down syndrome is discussed Conclusion: A positive association between Down syndrome and retinoblastoma is possible An epidemiological study on this subject is needed to better ascertain this potential link

Molecular characterization of the deletion in retinoblastoma patients with 13q14 cytogenetic anomalies.

Abstract: We investigated the molecular deletions of twelve patients presenting with retinoblastoma and a cytogenetic abnormality including band 13q14. Dinucleotide markers spanning the complete chromosome 13 as well as two intragenic markers were analyzed in patients and their two parents. The deletion was considered confirmed when one heterozygous allele was missing, potential when a homozygous allele was observed in continuity with a clearly deleted allele, and noninformative when a homozygous allele was observed adjacent to a nondeleted region. The patients could be classified into three groups based on their cytogenetic abnormalities. In group 1, the cytogenetic deletion was restricted to band13q14 with confirmed or potential molecular deletions extending from D13S328 to D13S153. Although a possible common centromeric deletion breakpoint could exist for three of the patients and a common telomeric deletion breakpoint for two, the cytogenetic deletion was different for most of them. Group 2 included patients with a cytogenetic deletion extending up to 13q22. At the molecular level, the telomeric breakpoints were between the RB1 gene and D13S156. Here again, it is quite unlikely that a common telomeric breakpoint was responsible for the deletion. Group 3 consisted of special cases with either a paracentric inversion or a complex translocation. The cytogenetic abnormalities around 13q14 correlate with the molecular deletions that were observed in this study. Associated malformations cannot be easily predicted from the size of the deletions.

EFEMP1 is not associated with sporadic early onset drusen

Abstract: The early onset of multiple drusen in the posterior pole of the retina is characteristic of a group of macular dystrophies often referred to as dominant or radial drusen. At least two forms, Doyne honeycomb retinal dystrophy (DHRD) and Malattia Leventinese (MLVT), are associated with a single missense mutation (R345W) in the gene encoding the EGF-containing fibulin-like extracellular matrix protein-1 (EFEMP1) and are now thought to represent a single entity. Here, we present a further evaluation of the role of EFEMP1 in the pathogenesis of sporadic forms of early onset drusen. We analyzed all coding exons of the EFEMP1 gene by SSCP analysis in 14 unrelated individuals with early onset of multiple drusen and no apparent family history of the disease. In this patient group, we did not detect the R345W mutation or any other disease-associated mutation. Three different polymorphisms and two intragenic polymorphic repeats were present in similar frequencies in the patients and control individuals. We conclude ...

Ocular findings in distal arthrogryposis

Abstract: (2001). Ocular findings in distal arthrogryposis. Ophthalmic Genetics: Vol. 22, No. 2, pp. 125-130.

Phenotype associated with an R120X nonsense mutation in the RP2 gene in a Japanese family with X-linked retinitis pigmentosa.

Abstract: We examined a Japanese family with X-linked retinitis pigmentosa (RP) associated with a nonsense mutation, R120X, in the RP2 gene. The 26-year-old proband presented at the age of seven years with a two-year history of night blindness. Visual disability worsened with increasing age. At age 24, visual acuity was 0.08 in both eyes. Testing for refractive error indicated mild myopia. Visual fields showed bilateral-constriction to 10 degrees. He had central macular areolar sclerosis in both eyes. Two maternal uncles had vision of light perception to hand movement in their early forties together with dense bilateral cataracts. The ocular phenotype of this family with R120X was considered severe; reported phenotypes associated with this mutation have not been uniform.

Evaluation of RLBP1 in 50 autosomal recessive retinitis pigmentosa and 4 retinitis punctata albescens Spanish families.

Abstract: Defects in retinal vitamin A metabolism or in genes expressed in the retinal pigment epithelium (RPE) are related to nonsyndromic retinitis pigmentosa (RP). The RLBP1 gene encodes the cellular retinaldehyde-binding protein which, in the RPE and Muller cells of the retina, is thought to play a role in retinoid metabolism and visual pigment regeneration. We describe a study of the involvement of the RLBP1 gene in 50 autosomal recessive retinitis pigmentosa (ARRP) and four retinitis punctata albescens Spanish families. Cosegregation and homozygosity studies using an intragenic polymorphism and three close markers (D15S116, D15S127, and D15S130) ruled out RLBP1 as the cause of ARRP in 26 pedigrees. In the remaining families, SSCP analysis of the coding region and sequencing of the abnormal migrating bands did not detect any disease-causing mutation. These results indicate that mutations in the RLBP1 gene are not responsible for the ARRP or retinitis punctata albescens in this set of Spanish families. We did, ...