Abstract
A gene responsible for facioscapulohumeral muscular dystrophy (FSHD) has been linked to polymorphisms on chromosome 4q35. Multipoint linkage analyses have placed this gene distal to all reported genetic markers on the chromosome. By using as a probe a clone isolated from a cosmid containing sequences related to a homeobox domain, de novo DNA rearrangements were reported in sporadic and familial cases of FSHD. Linkage analysis of an EcoRI polymorphism detected by this clone in twenty–four multigenerational FSHD families revealed recombinants between this marker and the disease with a recombination fraction of 0.05. Two families with apparent germline mosaicism were also identified.
This is a preview of subscription content, access via your institution
Access options
Subscribe to this journal
Receive 12 print issues and online access
$209.00 per year
only $17.42 per issue
Rent or buy this article
Prices vary by article type
from$1.95
to$39.95
Prices may be subject to local taxes which are calculated during checkout
Similar content being viewed by others
References
Lunt, P.W., Compston, D.A.S. & Harper, P.S. Estimation of age dependent penetrance in facioscapulohumeral muscular dystrophy by minimising ascertainment bias. J. med. Genet. 26, 755–760 (1989).
Wijmenga, C. et al. Location of the facioscapulohumeral muscular dystrophy gene on chromosome 4. Lancet 336, 651–653 (1990).
Sarfarazi, M. et al. Regional mapping of facioscapulohumeral muscular dystrophy gene on 4q35: combined analysis of an international consortium. Am. J. hum. Genet. 51, 396–403 (1992).
Wijmenga, C. et al. Chromosome 4q DNA rearrangements associated with acioscapulohumeral muscular dystrophy. Nature Genet. 2, 26– (1992).
Weiffenbach, B. et al. Linkage analyses of five chromosome 4 markers localizes the facioscapulohumeral muscular dystrophy (FSHD) gene to distal 4q35. Am. J. hum. Genet. 51, 416–423 (1992).
Weiffenbach, B. et al. Framework multipoint map of the long arm of human chromosome 4 and telomeric localization of the gene for FSHD. Mamm. Genome 3, 143–150 (1992).
Schellenberg, G.D. et al. Genetic linkage evidence for a familial Alzheimer's disease locus on chromosome 14. Science 268, 668–671 (1992).
Smith, C.A.B. Testing for heterogeneity of recombination fraction values in human genetics. Ann. hum. Genet 27, 175–182 (1963).
Ott, J. Analysis of Human Genetic Linkage 203–213 (Johns Hopkins University Press, Baltimore, 1991).
Lupski, J.R. et al. DNA duplication associated with Charcot-Marie-Tooth disease type 1A. Cell 66, 219–232 (1991).
Koenig, M. et al. Complete cloning of the Duchenne muscular dystrophy (DMD) cDNA and preliminary genomic organization of the DMD gene in normal and affected individuals. Cell 50, 509–517 (1987).
Murray, E.W., Giles, A.R. & Lillicrap, D. Germ-line mosaicism for a valine-to-methionine substitution at residue 553 in the glycoprotein Ib-binding domain of von Willebrand factor, causing type MB von Willebrand disease. Am. J. hum. Genet. 50, 199–207 (1992).
Cohn, D.H., Starman, B.J., Blumberg, B. & Byers, P.H. Recurrence of lethal osteogenesis imperfecta due to parental mosaicism for a dominant mutation in a human type I collagen gene (COLIAI). Am. J. hum. Genet. 46, 591–601 (1990).
Lanman, J.T. et al. Familial inheritance of a DXS164-deletion mutation from a heterozygous female. Am. J. hum. Genet. 41, 138–144 (1987).
Monaco, A.P., Bertelson, C.J., Colletti-Feener, C. & Kunkel, L.M. Localization and cloning of Xp21 deletion breakpoints involved in muscular dystrophy. Hum. Genet. 75, 221–227 (1987).
Bakker, E. et al. Germline mosaicism and Duchenne muscular dystrophy mutations. Nature 329, 554–556 (1987).
Darras, B.T. & Franke, U. A partial deletion of the muscular dystrophy gene transmitted twice by an unaffected male. Nature 329, 556–558 (1987).
Wood, S. & MacGillivray, B.C. Germinal mosaicism in Duchenne muscular dystrophy. Hum. Genet. 78, 282–284 (1987).
Griggs, R.C. et al. Facioscapulohumeral dystrophy: Evidence for new mutations. Neurology (in the press).
Jacobsen, S.J. et al. A clinically homogeneous group of families with Facioscapulohumeral (Landouzy-Dejerine) muscular dystrophy: Linkage analysis of six autosomes. Am. J. hum. Genet. 47, 376–388 (1990).
Gilbert, J.R. et al. Linkage studies in Facioscapulohumeral muscular dystrophy (FSHD). Am. J. hum. Genet. 51, 424–427 (1992).
Tyler, F.H. & Stephens, F.E. Studies in disorders of muscle. II Clinical manifestations and inheritance of facioscapulohumeral dystrophy in a large family. Ann. intern. Med. 32, 640–660 (1950).
vanDilla, M.A. et al. Human chromosome-specific DNA libraries:Construction and availability. Biotechnology 4, 537–552 (1986).
Nichols, R.D. et al. High resolution gene mapping of the human alpha globin locus. J. med. Genet. 24, 39–46 (1987).
Donis-Keller, H. et al. A genetic linkage map of the human genome. Cell 51, 319–337 (1987).
Mariat, D., Lauthier, V. & Vergnaud, G. A VNTR isolated by size selection of human DNA fragments detects RFLPs at the extremity of 1p and 4q. Nucl. Acids Res. 19, 4572.
Carle, G.F. et al. Electrophoretic separations of large DNA molecules by periodic inversion of the electric field. Science 232, 65–68 (1986).
Feinberg, A.P. & Vogelstein, B. A technique for radiolabeling DNA restriction endonuclease fragments to high specific activity. Anal. Biochem. 132, 6–13 (1983).
Author information
Authors and Affiliations
Rights and permissions
About this article
Cite this article
Weiffenbach, B., Dubois, J., Storvick, D. et al. Mapping the facioscapulohumeral muscular dystrophy gene is complicated by chromosome 4q35 recombination events. Nat Genet 4, 165–169 (1993). https://doi.org/10.1038/ng0693-165
Received:
Accepted:
Issue Date:
DOI: https://doi.org/10.1038/ng0693-165
This article is cited by
-
Analysis of the organisation and localisation of the FSHD-associated tandem array in primates: Implications for the origin and evolution of the 3.3 kb repeat family
Chromosoma (1996)
-
The DNA rearrangement associated with facioscapulohumeral muscular dystrophy involves a heterochromatin-associated repetitive element: Implications for a role of chromatin structure in the pathogenesis of the disease
Chromosome Research (1994)
-
Framework multipoint map of the long arm of human Chromosome 4 and telomeric localization of the gene for FSHD
Mammalian Genome (1992)