Linkage to D3S47 (C17) in one large autosomal dominant retinitis pigmentosa family and exclusion in another: confirmation of genetic heterogeneity

Douglas H. Lester, C F Inglehearn, R Bashir, H Ackford, L Esakowitz, M Jay, A C Bird, A F Wright, S S Papiha, S S Bhattacharya

    Research output: Contribution to journalArticle

    13 Citations (Scopus)

    Abstract

    Recently Dryja and his co-workers observed a mutation in the 23d codon of the rhodopsin gene in a proportion of autosomal dominant retinitis pigmentosa (ADRP) patients. Linkage analysis with a rhodopsin-linked probe C17 (D3S47) was carried out in two large British ADRP families, one with diffuse-type (D-type) RP and the other with regional-type (R-type) RP. Significantly positive lod scores (lod score maximum [Zmax] = +5.58 at recombination fraction [theta] = .0) were obtained between C17 and our D-type ADRP family showing complete penetrance. Sequence and oligonucleotide analysis has, however, shown that no point mutation at the 23d codon exists in affected individuals in our complete-penetrance pedigree, indicating that another rhodopsin mutation is probably responsible for ADRP in this family. Significantly negative lod scores (Z less than -2 at theta = .045) were, however, obtained between C17 and our R-type family which showed incomplete penetrance. Previous results presented by this laboratory also showed no linkage between C17 and another large British R-type ADRP family with incomplete penetrance. This confirms genetic heterogeneity. Some types of ADRP are being caused by different mutations in the rhodopsin locus (3q21-24) or another tightly linked gene in this region, while other types of ADRP are the result of mutations elsewhere in the genome.

    Original languageEnglish
    Pages (from-to)536-541
    Number of pages6
    JournalAmerican Journal of Human Genetics
    Volume47
    Issue number3
    Publication statusPublished - Sep 1990

      Fingerprint

    Cite this

    Lester, D. H., Inglehearn, C. F., Bashir, R., Ackford, H., Esakowitz, L., Jay, M., ... Bhattacharya, S. S. (1990). Linkage to D3S47 (C17) in one large autosomal dominant retinitis pigmentosa family and exclusion in another: confirmation of genetic heterogeneity. American Journal of Human Genetics, 47(3), 536-541.