Novel GUCA1A Mutations Suggesting Possible Mechanisms of Pathogenesis in Cone, Cone-Rod, and Macular Dystrophy Patients.
Here, we report two novel GUCA1A (the gene for guanylate cyclase activating protein 1) mutations identified in unrelated Spanish families affected by autosomal dominant retinal degeneration (adRD) with cone and rod involvement. All patients from a three-generation adRD pedigree underwent detailed op...
| Published in: | BioMed Research International Vol. 2013; pp. 517570 - 517571 |
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| Main Authors: | , , , , , , , , , |
| Format: | Journal Article |
| Published: |
Wiley-Blackwell
2013
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| Online Access: | View this record in EBSCOhost |
| fields | @attributes: recordID: 1 pdfLink: plink: https://search.ebscohost.com/login.aspx?direct=true&db=ccm&AN=104094546&site=ehost-live header: @attributes: shortDbName: ccm uiTerm: 104094546 longDbName: CINAHL Complete uiTag: AN controlInfo: bkinfo: dissinfo: jinfo: jid: 23146133 FT2T jtl: BioMed Research International issn: 23146133 maglogo: N pubinfo: dt: 2013 vid: 2013 pid: 480 pub: Wiley-Blackwell place: Malden, Massachusetts artinfo: ui: 104094546 2012258995 NLM24024198 PMC3759255 104094546 ppf: 517570 ppct: 1 formats: fmt: @attributes: type: P tig: atl: Novel GUCA1A Mutations Suggesting Possible Mechanisms of Pathogenesis in Cone, Cone-Rod, and Macular Dystrophy Patients. aug: au: Kamenarova, Kunka Corton, Marta García-Sandoval, Blanca Fernández-San Jose, Patricia Panchev, Valentin Avila-Fernández, Almudena López-Molina, Maria Isabel Chakarova, Christina Ayuso, Carmen Bhattacharya, Shomi S affil: Department of Cellular Therapy and Regenerative Medicine, Andalusian Centre for Molecular Biology and Regenerative Medicine (CABIMER), 'Isla Cartuja', 41092 Seville, Spain. sug: subj: Genetics Macular Degeneration Retinal Diseases Female Genome, Human Macular Degeneration Pathology Male Mutation Pedigree Photoreceptors Pathology Polymorphism, Genetic Retinal Diseases Physiopathology Retinitis Pigmentosa Retinitis Pigmentosa Pathology Female Male ab: Here, we report two novel GUCA1A (the gene for guanylate cyclase activating protein 1) mutations identified in unrelated Spanish families affected by autosomal dominant retinal degeneration (adRD) with cone and rod involvement. All patients from a three-generation adRD pedigree underwent detailed ophthalmic evaluation. Total genome scan using single-nucleotide polymorphisms and then the linkage analysis were undertaken on the pedigree. Haplotype analysis revealed a 55.37 Mb genomic interval cosegregating with the disease phenotype on chromosome 6p21.31-q15. Mutation screening of positional candidate genes found a heterozygous transition c.250C>T in exon 4 of GUCA1A, corresponding to a novel mutation p.L84F. A second missense mutation, c.320T>C (p.I107T), was detected by screening of the gene in a Spanish patients cohort. Using bioinformatics approach, we predicted that either haploinsufficiency or dominant-negative effect accompanied by creation of a novel function for the mutant protein is a possible mechanism of the disease due to c.250C>T and c.320T>C. Although additional functional studies are required, our data in relation to the c.250C>T mutation open the possibility that transacting factors binding to de novo created recognition site resulting in formation of aberrant splicing variant is a disease model which may be more widespread than previously recognized as a mechanism causing inherited RD. pubtype: Academic Journal doctype: Journal Article ougenre: Article language: English refInfo: holdings: @attributes: islocal: N |
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