Assignment of Emery-Dreifuss muscular dystrophy to the distal region of Xq28: the results of a collaborative study.
Emery-Dreifuss muscular dystrophy (EDMD) is an X-linked humeroperoneal dystrophy associated with cardiomyopathy that is distinct from the Duchenne and Becker forms of X-linked muscular dystrophy. Linkage analysis has assigned EDMD to the terminal region of the human X chromosome long arm. We report here further linkage analysis in two multigenerational EDMD families using seven Xq28 marker loci. Cumulative lod scores suggest that EDMD is approximately 2 cM from DXS52 (lod = 15.67) and very close to the factor VIII (F8C) and the red/green color pigment (R/GCP) loci, with respective lod scores of 9.62 and 10.77, without a single recombinant. Several recombinations between EDMD and three proximal Xq28 markers suggest that the EDMD gene is located in distal Xq28. Multipoint linkage analysis indicates that the odds are 2,000:1 that EDMD lies distal to DXS305. These data substantially refine the ability to perform accurate carrier detection, prenatal diagnosis, and the presymptomatic diagnosis of at-risk males for EDMD by linkage analysis. The positioning of the EDMD locus close to the loci for F8C and R/GCP will assist in future efforts to identify and isolate the disease gene.
Consalez
G G
GG
Department of Biochemistry, Emory University School of Medicine, Atlanta, GA 30322.
Thomas
N S
NS
Stayton
C L
CL
Knight
S J
SJ
Johnson
M
M
Hopkins
L C
LC
Harper
P S
PS
Elsas
L J
LJ
Warren
S T
ST
D002874:Chromosome Mapping; D004247:DNA / Q000032:analysis; D005260:Female; D006580:Genetic Carrier Screening; D008040:Genetic Linkage; D005819:Genetic Markers; D005820:Genetic Testing; D006801:Humans; D008297:Male; D009136:Muscular Dystrophies / Q000175:diagnosis / Q000235:genetics*; D020389:Muscular Dystrophy, Emery-Dreifuss; D010375:Pedigree; D011110:Polymorphism, Genetic; D012307:Risk Factors; D014960:X Chromosome / Q000648:ultrastructure*
D005819:Genetic Markers; D004247:DNA