Novel locus for autosomal recessive cone-rod dystrophy CORDS mapping to chromosome 1q12-q24

Citation
S. Khaliq et al., Novel locus for autosomal recessive cone-rod dystrophy CORDS mapping to chromosome 1q12-q24, INV OPHTH V, 41(12), 2000, pp. 3709-3712
Citations number
16
Language
INGLESE
art.tipo
Article
Categorie Soggetti
da verificare
Journal title
INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE
ISSN journal
0146-0404 → ACNP
Volume
41
Issue
12
Year of publication
2000
Pages
3709 - 3712
Database
ISI
SICI code
0146-0404(200011)41:12<3709:NLFARC>2.0.ZU;2-7
Abstract
PURPOSE. To map the disease locus of a two-generation, consanguineous Pakis tani family with autosomal recessive cone-rod dystrophy (arCRD). All affect ed individuals had night blindness, deterioration of central vision, photop hobia, epiphora in bright light, and problems with color distinction. Fundo scopy revealed marked macular degeneration and attenuation of retinal vesse ls. Mild pigmentary changes were present in the periphery. METHODS. Genomic DNA was amplified across the polymorphic microsatellite po ly-CA regions identified by markers. Alleles were assigned to individuals t hat allowed calculation of LOD scores using the Cyrillic (Cherwell Scientif ic, Oxford, UK) and MLINK (accessed from ftp://linkage. rockefeller.edu/sof teware/linkage/) software programs. The cellular retinoic acid-binding prot ein 2 (CRABP2), cone transducin alpha -subunit (GNAT2), potassium inwardly rectifying channel, subfamily J, member 10 (KCNJ10), genes were analyzed by heteroduplex analysis and direct sequencing for mutations. RESULTS. A new locus for arCRD (CORD8) has been mapped to chromosome 1q12-q 24. A maximum two-point LOD score of 4.22 was obtained with marker D1S2635 at recombination fraction of theta = 0.00. Two critical recombinations in t he pedigree positioned this locus to a region flanked by markers D1S457 and D1S2681. A region of homozygosity was observed within the loci D1S442 and D1S2681, giving a probable critical disease interval of 21 cM. Mutation scr eening of the three candidate genes CRABP2, GNAT2, and KCNJ10 revealed no d isease-associated mutations. CONCLUSIONS. The findings therefore suggest that this phenotype maps to a n ew locus and is due to an as yet uncharacterized gene within the 1q12-q24 c hromosomal region.