CONGENITAL FIBROSIS OF THE EXTRAOCULAR-MUSCLES (AUTOSOMAL-DOMINANT CONGENITAL EXTERNAL OPHTHALMOPLEGIA) - GENETIC HOMOGENEITY, LINKAGE REFINEMENT, AND PHYSICAL MAPPING ON CHROMOSOME-12

EC ENGLE*, [No Value] MARONDEL, WA HOUTMAN, B DEVRIES, A LOEWENSTEIN, M LAZAR, DC WARD, R KUCHERLAPATI, AH BEGGS

*Corresponding author for this work

    Research output: Contribution to journalArticleAcademicpeer-review

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    Abstract

    Congenital fibrosis of the extraocular muscles (CFEOM) is an autosomal dominant syndrome of congenital external ophthalmoplegia and bilateral ptosis. We previously reported linkage of this disorder in two unrelated families to an 8-cM region near the centromere of human chromosome 12. We now present refinement of linkage in the original two families, linkage analysis of five additional families, and a physical map of the critical region for the CFEOM gene. In each of the seven families the disease gene is linked to the pericentromeric region of chromosome 12. D12S345, D12S59, D12S331, and D12S1048 do not recombine with the disease gene and have combined lod scores of 35.7, 35.6, 16.0, and 31.4, respectively. AFM136xf6 and AFMb320wd9 flank the CFEOM locus, defining a critical region of 3 cM spanning the centromere of chromosome 12. These data support the concept that this may be a genetically homogeneous disorder. We also describe the generation of a YAC contig encompassing the critical region of the CFEOM locus. This interval has been assigned cytogenetically to 12p11.2-q12 and spans the centromere of chromosome 12. These results provide the basis for further molecular analyses of the structure and organization of the CFEOM locus and will help in the identification of candidate genes.

    Original languageEnglish
    Pages (from-to)1086-1094
    Number of pages9
    JournalAmerican Journal of Human Genetics
    Volume57
    Issue number5
    Publication statusPublished - Nov-1995

    Keywords

    • INSITU HYBRIDIZATION
    • CLONES
    • SEQUENCES
    • DNA

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