PURPOSE: To map the disease locus of a two-generation, consanguineous Pakistani family with autosomal recessive cone-rod dystrophy (arCRD). All affected individuals had night blindness, deterioration of central vision, photophobia, epiphora in bright light, and problems with color distinction. Fundoscopy revealed marked macular degeneration and attenuation of retinal vessels. Mild pigmentary changes were present in the periphery. METHODS: Genomic DNA was amplified across the polymorphic microsatellite poly-CA regions identified by markers. Alleles were assigned to individuals that allowed calculation of LOD scores using the Cyrillic (Cherwell Scientific, Oxford, UK) and MLINK (accessed from ftp://linkage. rockefeller.edu/softeware/linkage/) software programs. The cellular retinoic acid-binding protein 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-q24. 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 the 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 screening of the three candidate genes CRABP2, GNAT2, and KCNJ10 revealed no disease-associated mutations. CONCLUSIONS: The findings therefore suggest that this phenotype maps to a new locus and is due to an as yet uncharacterized gene within the 1q12-q24 chromosomal region.
PURPOSE: To map the disease locus of a two-generation, consanguineous Pakistani family with autosomal recessive cone-rod dystrophy (arCRD). All affected individuals had night blindness, deterioration of central vision, photophobia, epiphora in bright light, and problems with color distinction. Fundoscopy revealed marked macular degeneration and attenuation of retinal vessels. Mild pigmentary changes were present in the periphery. METHODS: Genomic DNA was amplified across the polymorphic microsatellite poly-CA regions identified by markers. Alleles were assigned to individuals that allowed calculation of LOD scores using the Cyrillic (Cherwell Scientific, Oxford, UK) and MLINK (accessed from ftp://linkage. rockefeller.edu/softeware/linkage/) software programs. The cellular retinoic acid-binding protein 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-q24. 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 the 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 screening of the three candidate genes CRABP2, GNAT2, and KCNJ10 revealed no disease-associated mutations. CONCLUSIONS: The findings therefore suggest that this phenotype maps to a new locus and is due to an as yet uncharacterized gene within the 1q12-q24 chromosomal region.
Authors: Karin W Littink; Robert K Koenekoop; L Ingeborgh van den Born; Rob W J Collin; Luminita Moruz; Joris A Veltman; Susanne Roosing; Marijke N Zonneveld; Amer Omar; Mahshad Darvish; Irma Lopez; Hester Y Kroes; Maria M van Genderen; Carel B Hoyng; Klaus Rohrschneider; Mary J van Schooneveld; Frans P M Cremers; Anneke I den Hollander Journal: Invest Ophthalmol Vis Sci Date: 2010-06-16 Impact factor: 4.799
Authors: Muhammad Ansar; Regie Lyn P Santos-Cortez; Muhammad Arif Nadeem Saqib; Fareeha Zulfiqar; Kwanghyuk Lee; Naeem Mahmood Ashraf; Ehsan Ullah; Xin Wang; Sundus Sajid; Falak Sher Khan; Muhammad Amin-ud-Din; Joshua D Smith; Jay Shendure; Michael J Bamshad; Deborah A Nickerson; Abdul Hameed; Saima Riazuddin; Zubair M Ahmed; Wasim Ahmad; Suzanne M Leal Journal: Hum Genet Date: 2015-06-11 Impact factor: 4.132
Authors: David A Parry; Carmel Toomes; Lina Bida; Michael Danciger; Katherine V Towns; Martin McKibbin; Samuel G Jacobson; Clare V Logan; Manir Ali; Jacquelyn Bond; Rebecca Chance; Steven Swendeman; Lauren L Daniele; Kelly Springell; Matthew Adams; Colin A Johnson; Adam P Booth; Hussain Jafri; Yasmin Rashid; Eyal Banin; Tim M Strom; Debora B Farber; Dror Sharon; Carl P Blobel; Edward N Pugh; Eric A Pierce; Chris F Inglehearn Journal: Am J Hum Genet Date: 2009-04-30 Impact factor: 11.025