title: DNA rearrangements in Japanese facioscapulohumeral muscular dystrophy patients: clinical correlations.
abstract: Facioscapulohumeral muscular dystrophy (FSHD) is an autosomal dominant muscular disorder in which the disease locus has been mapped to chromosome 4q35-qter. In most patients, the DNA rearrangements associated with FSHD have been found in the EcoRI fragment detected by the p13E-11 probe, and deletions of the 3.2 kb repeat units within the fragment are thought to cause the disease. To examine FSHD-associated DNA rearrangements in the Japanese population, we performed Southern blot analysis of the genomic DNA, using the p13E-11 and pFR-1 probes, in 158 Japanese individuals, including 38 FSHD patients from 19 families. We found that all but one (a possible affected recombinant) of the Japanese FSHD patients (97.4%) had specific smaller (< 28 kb) EcoRI fragments which cosegregated with the disease; this included four patients who had severe inflammatory changes in the muscle and eight patients with de novo DNA rearrangements. We found no FSHD patient who had a fragment larger than 28 kb. By contrast, only two of 35 Japanese controls (5.7%) had EcoRI fragments smaller than 28 kb. Our patients showed anticipation, i.e. decreased size of the EcoRI fragment in parallel with earlier onset of the disease (r = 0.531, P = 0.003, with younger age at onset in children (17.8 +/- 7.0) than their affected parents (31.5 +/- 14.8) (P = 0.019). However, since each family had a specific small EcoRI fragment associated with the disease, the differing clinical severity within a family cannot be explained by the size of the fragment alone.(ABSTRACT TRUNCATED AT 250 WORDS)
authors.affiliation: National Institute of Neuroscience, NCNP, Tokyo, Japan.
authors.forename: K
authors.initials: K
authors.lastname: Goto
authors.forename: J H
authors.initials: JH
authors.lastname: Lee
authors.forename: C
authors.initials: C
authors.lastname: Matsuda
authors.forename: K
authors.initials: K
authors.lastname: Hirabayashi
authors.forename: T
authors.initials: T
authors.lastname: Kojo
authors.forename: A
authors.initials: A
authors.lastname: Nakamura
authors.forename: Y
authors.initials: Y
authors.lastname: Mitsunaga
authors.forename: T
authors.initials: T
authors.lastname: Furukawa
authors.forename: K
authors.initials: K
authors.lastname: Sahashi
authors.forename: K
authors.initials: K
authors.lastname: Arahata
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D002648:Child; D002675:Child, Preschool; D002874:Chromosome Mapping; D004247:DNA / Q000032:analysis*; D015342:DNA Probes; D005260:Female; D015321:Gene Rearrangement / Q000235:genetics*; D008040:Genetic Linkage; D006801:Humans; D006811:Humerus; D007223:Infant; D007231:Infant, Newborn; D007564:Japan; D008126:Lod Score; D008297:Male; D008875:Middle Aged; D009136:Muscular Dystrophies / Q000235:genetics*; D010375:Pedigree; D015183:Restriction Mapping; D012540:Scapula
chemical_list: D015342:DNA Probes; D004247:DNA