title: Identification of a locus on chromosome 2q11 at which recessive amelogenesis imperfecta and cone-rod dystrophy cosegregate.
abstract: A consanguineous Arab pedigree in which recessive amelogenesis imperfecta (AI) and cone-rod dystrophy cosegregate, was screened for linkage to known retinal dystrophy and tooth abnormality loci by genotyping neighbouring microsatellite markers. This analysis resulted in linkage with a maximum lod score of 7.03 to the marker D2S2187 at the achromatopsia locus on chromosome 2q11, and haplotype analysis placed the gene(s) involved in a 2 cM/5 Mb interval between markers D2S2209 and D2S373. The CNGA3 gene, known to be involved in achromatopsia, lies in this interval but thorough analysis of its coding sequence revealed no mutation. Furthermore, affected individuals in four consanguineous recessive pedigrees with AI but without CRD were heterozygous at this locus, excluding it as a common cause of non-syndromic recessive AI. It remains to be established whether this pedigree is segregating two closely linked mutations causing disparate phenotypes or whether a single defect is causing pathology in both teeth and eyes.
authors.affiliation: Molecular Medicine Unit, CSB, St James's University Hospital, Leeds University, Leeds LS9 7TF UK.
authors.forename: Louise M
authors.initials: LM
authors.lastname: Downey
authors.forename: T Jeffrey
authors.initials: TJ
authors.lastname: Keen
authors.forename: Ismail K
authors.initials: IK
authors.lastname: Jalili
authors.forename: John
authors.initials: J
authors.lastname: McHale
authors.forename: Michael J
authors.initials: MJ
authors.lastname: Aldred
authors.forename: Steven P
authors.initials: SP
authors.lastname: Robertson
authors.forename: Alan
authors.initials: A
authors.lastname: Mighell
authors.forename: Steven
authors.initials: S
authors.lastname: Fayle
authors.forename: Bernd
authors.initials: B
authors.lastname: Wissinger
authors.forename: Chris F
authors.initials: CF
authors.lastname: Inglehearn
mesh_terms: D000567:Amelogenesis Imperfecta / Q000235:genetics*; D001483:Base Sequence; D002874:Chromosome Mapping; D002889:Chromosomes, Human, Pair 2 / Q000235:genetics*; D054815:Cyclic Nucleotide-Gated Cation Channels; D004252:DNA Mutational Analysis; D005260:Female; D005808:Genes, Recessive / Q000235:genetics*; D006801:Humans; D007473:Ion Channels / Q000235:genetics; D008126:Lod Score; D008297:Male; D008969:Molecular Sequence Data; D010375:Pedigree; D012174:Retinitis Pigmentosa / Q000235:genetics*
chemical_list: D054815:Cyclic Nucleotide-Gated Cation Channels; D007473:Ion Channels