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Progress in the molecular diagnosis of facioscapulohumeral muscular dystrophy and correlation between the number of Kpn I repeats at the 4q35 locus and clinical phenotype
Author(s) -
Ricci E.,
Galluzzi G.,
Deidda G.,
Cacurri S.,
Colantoni L.,
Merico B.,
Piazzo N.,
Servidei S.,
Vigneti E.,
Pasceri V.,
Silvestri G.,
Mirabella M.,
Mangiola F.,
Tonali P.,
Felicetti L.
Publication year - 1999
Publication title -
annals of neurology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 4.764
H-Index - 296
eISSN - 1531-8249
pISSN - 0364-5134
DOI - 10.1002/1531-8249(199906)45:6<751::aid-ana9>3.0.co;2-m
Subject(s) - ecori , facioscapulohumeral muscular dystrophy , genetics , restriction fragment length polymorphism , locus (genetics) , biology , phenotype , restriction fragment , genotype , muscular dystrophy , restriction enzyme , microbiology and biotechnology , medicine , gene
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. Eco RI— Bln I double digestion was routinely used to avoid the interference of small Eco RI fragments of 10qter origin that were found in 15% of the controls. An Eco RI fragment ranging between 10 and 28 kb that was resistant to Bln I 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 Eco RI 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 Eco RI fragment size of 10 to 13 kb (1–2 Kpn I repeats left), in 53% of patients with a fragment size of 16 to 20 kb (3–4 Kpn I repeats left), and in 19% of patients with a fragment size larger than 21 kb (>4 Kpn I 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. Ann Neurol 1999;45:751–757