title: Novel locus for autosomal recessive cone-rod dystrophy CORD8 mapping to chromosome 1q12-Q24.
abstract: OBJECTIVE
  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.affiliation: Dr. A.Q. Khan Research Laboratories, Biomedical and Genetic Engineering Division, Islamabad, Pakistan.
authors.forename: S
authors.initials: S
authors.lastname: Khaliq
authors.forename: A
authors.initials: A
authors.lastname: Hameed
authors.forename: M
authors.initials: M
authors.lastname: Ismail
authors.forename: K
authors.initials: K
authors.lastname: Anwar
authors.forename: B P
authors.initials: BP
authors.lastname: Leroy
authors.forename: S Q
authors.initials: SQ
authors.lastname: Mehdi
authors.forename: A M
authors.initials: AM
authors.lastname: Payne
authors.forename: S S
authors.initials: SS
authors.lastname: Bhattacharya
mesh_terms: D000293:Adolescent; D002648:Child; D002874:Chromosome Mapping; D002878:Chromosomes, Human, Pair 1 / Q000235:genetics*; D003117:Color Vision Defects / Q000235:genetics; D003241:Consanguinity; D004247:DNA / Q000032:analysis; D005260:Female; D008040:Genetic Linkage; D006801:Humans; D007766:Lacrimal Apparatus Diseases / Q000235:genetics; D008297:Male; D018895:Microsatellite Repeats; D009755:Night Blindness / Q000235:genetics; D010375:Pedigree; D020795:Photophobia / Q000235:genetics; D020419:Photoreceptor Cells, Vertebrate / Q000473:pathology*; D015221:Potassium Channels / Q000235:genetics; D024661:Potassium Channels, Inwardly Rectifying; D018168:Receptors, Retinoic Acid / Q000235:genetics; D012162:Retinal Degeneration / Q000235:genetics* / Q000473:pathology; D015293:Transducin / Q000235:genetics
chemical_list: D015221:Potassium Channels; D024661:Potassium Channels, Inwardly Rectifying; D018168:Receptors, Retinoic Acid; C082928:retinoic acid binding protein II, cellular; D004247:DNA; D015293:Transducin