title: Candidate-gene testing for orphan limb-girdle muscular dystrophies.
abstract: The term limb-girdle muscular dystrophies (LGMD) identify about two dozens of distinct genetic disorders. Additional genes must play a role, since there are LGMD families excluded from any known locus. The aim of our work is to test a number of candidate genes in unclassified LGMD patient and control DNA samples. We selected the following 11 candidate genes: myozenin 1, 2 and 3, gamma-filamin, kinectin-1, enolase-3 beta, ZASP, TRIM 11 and TRIM 17, OZZ and zeta-sarcoglycan. These candidates were chosen for a combination of different reasons: chromosomal position, sequence homology, interaction properties or muscular dystrophy phenotypes in animal models. The exon and flanking intron sequences were subjected to molecular testing by comparative mutation scanning by HT-DHPLC of LGMD patients versus control. We identified a large number of variations in any of the genes in both patients and controls. Correlations with disease or possible modifying effects on the LGMD phenotype remain to be investigated.
authors.affiliation: Telethon Institute of Genetics and Medicine (TIGEM), Naples, Italy.
authors.forename: S
authors.initials: S
authors.lastname: Aurino
authors.forename: G
authors.initials: G
authors.lastname: Piluso
authors.forename: V
authors.initials: V
authors.lastname: Saccone
authors.forename: M
authors.initials: M
authors.lastname: Cacciottolo
authors.forename: F
authors.initials: F
authors.lastname: D'Amico
authors.forename: M
authors.initials: M
authors.lastname: Dionisi
authors.forename: A
authors.initials: A
authors.lastname: Totaro
authors.forename: A
authors.initials: A
authors.lastname: Belsito
authors.forename: U
authors.initials: U
authors.lastname: Di Vicino
authors.forename: V
authors.initials: V
authors.lastname: Nigro
mesh_terms: D048868:Adaptor Proteins, Signal Transducing / Q000235:genetics; D002352:Carrier Proteins / Q000235:genetics*; D016022:Case-Control Studies; D015331:Cohort Studies; D003285:Contractile Proteins / Q000235:genetics*; D064448:Filamins; D020869:Gene Expression Profiling; D005820:Genetic Testing / Q000379:methods*; D006801:Humans; D060588:LIM Domain Proteins; D008565:Membrane Proteins / Q000235:genetics*; D008840:Microfilament Proteins / Q000235:genetics*; D009124:Muscle Proteins / Q000235:genetics*; D049288:Muscular Dystrophies, Limb-Girdle / Q000235:genetics*; D009154:Mutation / Q000235:genetics*; D010751:Phosphopyruvate Hydratase / Q000235:genetics; D049031:Sarcoglycans / Q000235:genetics; D000070584:Tripartite Motif Proteins; D043743:Ubiquitin-Protein Ligase Complexes; D044767:Ubiquitin-Protein Ligases / Q000235:genetics
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D002352:Carrier Proteins; D003285:Contractile Proteins; D064448:Filamins; C088547:KTN1 protein, human; C120696:LDB3 protein, human; D060588:LIM Domain Proteins; C419780:MYOZ1 protein, human; C419779:MYOZ2 protein, human; D008565:Membrane Proteins; D008840:Microfilament Proteins; D009124:Muscle Proteins; C483082:NEURL2 protein, human; D049031:Sarcoglycans; D000070584:Tripartite Motif Proteins; D043743:Ubiquitin-Protein Ligase Complexes; C510874:TRIM11 protein, human; C115437:TRIM17 protein, human; D044767:Ubiquitin-Protein Ligases; D010751:Phosphopyruvate Hydratase