| 1. |
- Burstedt, Marie Si, et al.
(author)
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Self-reported quality of life in patients with retinitis pigmentosa and maculopathy of Bothnia type.
- 2010
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In: Clinical ophthalmology (Auckland, N.Z.). - 1177-5467. ; 4, s. 147-154
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Journal article (peer-reviewed)abstract
- PURPOSE: To assess vision-related quality-of-life subscales with objective measurements of visual function in patients affected with retinitis pigmentosa of Bothnia type (BD). METHODS: Forty-nine patients answered the NEI-VFQ-25 questionnaire. High- and low-contrast distance acuity (VA), near VA, and visual fields (VF) were measured. Weighted VA (WVA) and low-contrast (10%) VA (WLCVA), binocular VF areas, and central scotoma were calculated. Adjusted mean subscale scores were calculated and associations analyzed. RESULTS: Subscale scores for general, far, and near vision, social functioning, and color vision were lowest while general health, ocular pain, and mental health were highest in the BD phenotype. The correlations were substantial and similar for WVA, WLCVA, and near vision. The degree of measured VF impairment had few associations with the different adjusted subscale scores. CONCLUSION: The NEI VFQ-25 subscales were well associated with clinical vision measures depending on VA. The progression of VF defects typical for the BD phenotype does not seem to affect the self-perceived quality of life, which might indicate adaptability to this type of progressive VF loss. The BD phenotype has a significant impact on multiple domains of daily life, but there are no signs of accelerating depression related to the increasing visual impairment.
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| 2. |
- Köhn, Linda, 1979-, et al.
(author)
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Breakpoint characterization of a novel ~59 kb genomic deletion on 19q13.42 in autosomal dominant retinitis pigmentosa with reduced penetrance
- 2009
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In: European Journal of Human Genetics. - : Nature publishing group. - 1018-4813 .- 1476-5438. ; 17:5, s. 651-655
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Journal article (peer-reviewed)abstract
- The aim of this study was to identify and characterize the underlying molecular mechanisms in autosomal-dominant retinitis pigmentosa (adRP) with incomplete penetrance in two Swedish families. An extended genealogical study and haplotype analysis indicated a common origin. Mutation identification was carried out by multiplex ligation-dependent probe amplification (MLPA) and sequencing. Clinical examinations of adRP families including electroretinography revealed obligate gene carriers without abnormalities, which indicated incomplete penetrance. Linkage analysis resulted in mapping of the disease locus to 19q13.42 (RP11). Sequence analyses did not reveal any mutations segregating with the disease in eight genes including PRPF31. Subsequent MLPA detected a large genomic deletion of 11 exons in the PRPF31 gene and, additionally, three genes upstream of the PRPF31. Breakpoints occurred in intron 11 of PRPF31 and in LOC441864, 'similar to osteoclast-associated receptor isoform 5.' An almost 59 kb deletion segregated with the disease in all affected individuals and was present in several asymptomatic family members but not in 20 simplex RP cases or 94 healthy controls tested by allele-specific PCR. A large genomic deletion resulting in almost entire loss of PRPF31 and three additional genes identified as the cause of adRP in two Swedish families provide an additional evidence that mechanism of the disease evolvement is haploinsufficiency. Identification of the deletion breakpoints allowed development of a simple tool for molecular testing of this genetic subtype of adRP.
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| 3. |
- Köhn, Linda, 1979-, et al.
(author)
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Carrier of R14W in carbonic anhydrase IV presents Bothnia dystrophy phenotype caused by two allelic mutations in RLBP1
- 2008
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In: Investigative Ophthalmology and Visual Science. - : Association for Research in Vision and Ophthalmology. - 0146-0404 .- 1552-5783. ; 49:7, s. 3172-3177
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Journal article (peer-reviewed)abstract
- Purpose: Bothnia dystrophy (BD) is an autosomal recessive retinitis pigmentosa (arRP) associated with the c.700C>T mutation in the RLBP1 gene. Testing of patients with BD has revealed the c.700C>T mutation on one or both alleles. The purpose of this study was to elucidate the underlying genetic mechanisms along with a clinical evaluation of the heterozygous patients with BD.Methods: Patients with BD heterozygous for the RLBP1 c.700C>T were tested for 848 mutations by arrayed primer-extension technology. Further mutation detection was performed by PCR-restriction fragment length polymorphism (RFLP), sequencing, denaturing (d)HLPC and allelic discrimination. The ophthalmic examinations were performed in all c.700C>T heterozygotes.Results: The clinical findings in 10 BD heterozygotes were similar to those in the homozygotes. The presence of a second mutation, c.677T>A, corresponding to p.M226K was detected in all 10 cases. Segregation analysis showed that the mutations were allelic, and the patients were compound heterozygotes [c.677T>A]+[c.700C>T]. One of those patients was also a carrier of the c.40C>T corresponding to the p.R14W change in carbonic anhydrase IV (CAIV) associated with autosomal dominant RP, RP17. His mother, a carrier of the identical change was declared healthy after ophthalmic examination. This sequence variant was found in 6 of 143 tested blood donors.Conclusions: The high frequency of arRP in northern Sweden is due to two mutations in the RLBP1 gene: c.677T>A and c.700C>T. BD is caused by the loss of CRALBP function due to changed physical features and impaired activity of retinoid binding. The CAIV p.R14W sequence variant found in one of the patients with a BD phenotype is a benign polymorphism in a population of northern Sweden.
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| 4. |
- Köhn, Linda, 1979-, et al.
(author)
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Mutation in the PYK2-binding domain of PITPNM3 causes autosomal dominant cone dystrophy (CORD5) in two Swedish families
- 2007
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In: European Journal of Human Genetics. - : Nature publishing group. - 1018-4813 .- 1476-5438. ; 15:6, s. 664-671
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Journal article (peer-reviewed)abstract
- Autosomal dominant cone dystrophy (CORD5) (MIM 600977) is a rare disease predominantly affecting cone photoreceptors. Here we refine the CORD5 locus previously mapped to 17p13 from 27 to 14.3 cM and identified a missense mutation, Q626H in the phosphatidylinositol transfer (PIT) membrane-associated protein (PITPNM3) (MIM 608921) in two Swedish families. PITPNM3, known as a human homologue of the Drosophila retinal degeneration B (rdgB), lacks the N-terminal PIT domain needed for transport of phospholipids, renewal of photoreceptors membrane and providing the electroretinogram (ERG) response to light. In our study, the mutation causing CORD5 is located in the C-terminal region interacting with a member of nonreceptor protein tyrosine kinases, PYK2. Our finding on the first mutation in the human homologue of Drosophila rdgB indicates novel pathways and a potential important role of the PITPNM3 in mammalian phototransduction.
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