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

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    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

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  • Cite this

    Lester, D. H., Inglehearn, C. F., Bashir, R., Ackford, H., Esakowitz, L., Jay, M., Bird, A. C., Wright, A. F., Papiha, S. S., & 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. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1683865/pdf/ajhg00093-0173.pdf