Carrier of R14W in carbonic anhydrase IV presents Bothnia dystrophy phenotype caused by two allelic mutations in RLBP1Visa övriga samt affilieringar
2008 (Engelska)Ingår i: Investigative Ophthalmology and Visual Science, ISSN 0146-0404, E-ISSN 1552-5783, Vol. 49, nr 7, s. 3172-3177Artikel i tidskrift (Refereegranskat) Published
Abstract [en]
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.
Ort, förlag, år, upplaga, sidor
Association for Research in Vision and Ophthalmology , 2008. Vol. 49, nr 7, s. 3172-3177
Nyckelord [en]
Adolescent, Adult, Aged, Aged; 80 and over, Alleles, Amino Acid Substitution, Arginine, Carbonic Anhydrase IV/*genetics, Carrier Proteins/*genetics, Child, Cytosine, Female, Fundus Oculi, Genes; Recessive, Heterozygote, Homozygote, Humans, Male, Middle Aged, Mutation, Phenotype, Retinitis Pigmentosa/*genetics/pathology/physiopathology, Thymine, Tryptophan
Nationell ämneskategori
Medicinsk genetik Oftalmologi
Forskningsämne
oftalmiatrik; genetik
Identifikatorer
URN: urn:nbn:se:umu:diva-26981DOI: 10.1167/iovs.07-1664ISI: 000257124000051Scopus ID: 2-s2.0-48249101247OAI: oai:DiVA.org:umu-26981DiVA, id: diva2:275378
2009-11-052009-11-052023-03-23Bibliografiskt granskad
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