title: Molecular analysis of LGMD-2B and MM patients: identification of novel DYSF mutations and possible founder effect in the Italian population.
abstract: Dysferlin, the protein product of the dysferlin gene (DYSF), has been shown to have a role in calcium-induced membrane fusion and repair. Dysferlin is absent or drastically reduced in patients with the following autosomal recessive disorders: limb-girdle muscular dystrophy type 2B (LGMD-2B), Miyoshi myopathy (MM) and distal anterior compartment myopathy. To date, less than 45 mutations have been described in DYSF and a wide inter- and intra-familial variation in clinical phenotype has been associated with the same mutation. This observation underlines the relevance of any new report describing genotype/phenotype correlations in dysferlinopathic patient and families. Here we present the results of clinical, biochemical and genetic analysis performed on one MM and three LGMD Italian families. By screening the entire coding region of DYSF, we identified three novel mutations (two missense substitutions and one frame shift microdeletion). The possible existence of a founder effect for the Arg959Trp mutation in the Italian population is discussed.
authors.affiliation: IRCCS E. Medea, Associazione La Nostra Famiglia, Via Don Luigi Monza 20, 23842 Bosisio Parini (LC), Italy. rcagliani@bp.lnf.it
authors.forename: R
authors.initials: R
authors.lastname: Cagliani
authors.forename: F
authors.initials: F
authors.lastname: Fortunato
authors.forename: R
authors.initials: R
authors.lastname: Giorda
authors.forename: C
authors.initials: C
authors.lastname: Rodolico
authors.forename: M C
authors.initials: MC
authors.lastname: Bonaglia
authors.forename: M
authors.initials: M
authors.lastname: Sironi
authors.forename: M G
authors.initials: MG
authors.lastname: D'Angelo
authors.forename: A
authors.initials: A
authors.lastname: Prelle
authors.forename: F
authors.initials: F
authors.lastname: Locatelli
authors.forename: A
authors.initials: A
authors.lastname: Toscano
authors.forename: N
authors.initials: N
authors.lastname: Bresolin
authors.forename: G P
authors.initials: GP
authors.lastname: Comi
mesh_terms: D000328:Adult; D000368:Aged; D001120:Arginine / Q000235:genetics; D004252:DNA Mutational Analysis; D000073939:Dysferlin; D005260:Female; D018703:Founder Effect; D016368:Frameshift Mutation / Q000235:genetics; D005820:Genetic Testing; D005838:Genotype; D006801:Humans; D007558:Italy; D008297:Male; D008565:Membrane Proteins; D008875:Middle Aged; D009124:Muscle Proteins / Q000172:deficiency* / Q000235:genetics*; D009135:Muscular Diseases / Q000235:genetics* / Q000378:metabolism; D009136:Muscular Dystrophies / Q000235:genetics* / Q000378:metabolism; D009154:Mutation / Q000235:genetics*; D020125:Mutation, Missense / Q000235:genetics; D010375:Pedigree; D010641:Phenotype; D014364:Tryptophan / Q000235:genetics
chemical_list: C114839:DYSF protein, human; D000073939:Dysferlin; D008565:Membrane Proteins; D009124:Muscle Proteins; D014364:Tryptophan; D001120:Arginine