title: Inheritance of a 38-kb fragment in apparently sporadic facioscapulohumeral muscular dystrophy.
abstract: Facioscapulohumeral dystrophy (FSHD) is an autosomal-dominant muscular disorder associated with a short (<35 kb) EcoRI/BlnI fragment resulting from deletion of an integral number of units of a 3.3-kb repeat located at 4q35. In this study, we determined fragment sizes separated by pulsed-field gel electrophoresis in a patient with an apparently sporadic case of FSHD and in his healthy family members. A 38-kb fragment was detected in the proband, in his older brother, and in their father. This finding prompted a clinical reevaluation of the father and brother. A subclinical phenotype restricted to abdominal muscle weakness was detected, and serum creatine kinase values were found to be elevated in both. The proband's brother also showed evidence of an independently occurring subtelomeric rearrangement of 4q35, which normally occurs in about 20% of the population. The identification of a "borderline" 38-kb EcoRI/BlnI fragment in an affected subject and his very mildly affected relatives extends the size range of disease alleles and expands existing data on the variable intrafamilial expressivity of FSHD. This study highlights the importance of a careful molecular and clinical analysis extended to family members of apparently sporadic cases with larger EcoRI/BlnI fragments for accurate diagnosis and appropriate genetic counseling in FSHD.
authors.affiliation: Medical Genetics Unit, Department of Molecular Biology, Policlinico "Le Scotte," viale Bracci 2, 53100 Siena, Italy.
authors.forename: F
authors.initials: F
authors.lastname: Vitelli
authors.forename: M
authors.initials: M
authors.lastname: Villanova
authors.forename: A
authors.initials: A
authors.lastname: Malandrini
authors.forename: M
authors.initials: M
authors.lastname: Bruttini
authors.forename: M
authors.initials: M
authors.lastname: Piccini
authors.forename: L
authors.initials: L
authors.lastname: Merlini
authors.forename: G
authors.initials: G
authors.lastname: Guazzi
authors.forename: A
authors.initials: A
authors.lastname: Renieri
mesh_terms: D000328:Adult; D002894:Chromosomes, Human, Pair 4 / Q000235:genetics*; D004247:DNA / Q000235:genetics; D016521:Electrophoresis, Gel, Pulsed-Field; D017353:Gene Deletion; D015321:Gene Rearrangement / Q000235:genetics; D006801:Humans; D008297:Male; D008875:Middle Aged; D020391:Muscular Dystrophy, Facioscapulohumeral / Q000235:genetics* / Q000503:physiopathology; D010375:Pedigree
chemical_list: D004247:DNA