title: Progress in the molecular diagnosis of facioscapulohumeral muscular dystrophy and correlation between the number of KpnI repeats at the 4q35 locus and clinical phenotype.
abstract: Genotype analysis by using the p13E-11 probe and other 4q35 polymorphic markers was performed in 122 Italian facioscapulohumeral muscular dystrophy families and 230 normal controls. EcoRI-BlnI double digestion was routinely used to avoid the interference of small EcoRI fragments of 10qter origin that were found in 15% of the controls. An EcoRI fragment ranging between 10 and 28 kb that was resistant to BlnI digestion was detected in 114 of 122 families (93%) comprising 76 familial and 38 isolated cases. Among the unaffected individuals, 3 were somatic mosaics and 7, carrying an EcoRI fragment larger than 20 kb, could be rated as nonpenetrant gene carriers. In a cohort of 165 patients with facioscapulohumeral muscular dystrophy we found an inverse correlation between fragment size and clinical severity. A severe lower limb involvement was observed in 100% of patients with an EcoRI fragment size of 10 to 13 kb (1-2 KpnI repeats left), in 53% of patients with a fragment size of 16 to 20 kb (3-4 KpnI repeats left), and in 19% of patients with a fragment size larger than 21 kb (>4 KpnI repeats left). Our results confirm that the size of the fragment is a major factor in determining the facioscapulohumeral muscular dystrophy phenotype and that it has an impact on clinical prognosis and genetic counseling of the disease.
authors.affiliation: Institute of Neurology, Catholic University, Centre for Neuromuscular Diseases, Rome, Italy.
authors.forename: E
authors.initials: E
authors.lastname: Ricci
authors.forename: G
authors.initials: G
authors.lastname: Galluzzi
authors.forename: G
authors.initials: G
authors.lastname: Deidda
authors.forename: S
authors.initials: S
authors.lastname: Cacurri
authors.forename: L
authors.initials: L
authors.lastname: Colantoni
authors.forename: B
authors.initials: B
authors.lastname: Merico
authors.forename: N
authors.initials: N
authors.lastname: Piazzo
authors.forename: S
authors.initials: S
authors.lastname: Servidei
authors.forename: E
authors.initials: E
authors.lastname: Vigneti
authors.forename: V
authors.initials: V
authors.lastname: Pasceri
authors.forename: G
authors.initials: G
authors.lastname: Silvestri
authors.forename: M
authors.initials: M
authors.lastname: Mirabella
authors.forename: F
authors.initials: F
authors.lastname: Mangiola
authors.forename: P
authors.initials: P
authors.lastname: Tonali
authors.forename: L
authors.initials: L
authors.lastname: Felicetti
mesh_terms: D000328:Adult; D002894:Chromosomes, Human, Pair 4 / Q000235:genetics*; D006801:Humans; D009136:Muscular Dystrophies / Q000235:genetics* / Q000503:physiopathology; D010375:Pedigree; D010641:Phenotype; D011379:Prognosis; D012307:Risk Factors; D020080:Tandem Repeat Sequences