title: Integrin alpha 7 beta 1 in muscular dystrophy/myopathy of unknown etiology.
abstract: To investigate the role of integrin alpha 7 in muscle pathology, we used a "candidate gene" approach in a large cohort of muscular dystrophy/myopathy patients. Antibodies against the intracellular domain of the integrin alpha 7A and alpha 7B were used to stain muscle biopsies from 210 patients with muscular dystrophy/myopathy of unknown etiology. Levels of alpha 7A and alpha 7B integrin were found to be decreased in 35 of 210 patients (approximately 17%). In six of these patients no integrin alpha 7B was detected. Screening for alpha 7B mutation in 30 of 35 patients detected only one integrin alpha 7 missense mutation (the mutation on the second allele was not found) in a patient presenting with a congenital muscular dystrophy-like phenotype. No integrin alpha 7 gene mutations were identified in all of the other patients showing integrin alpha 7 deficiency. In the process of mutation analysis, we identified a novel integrin alpha 7 isoform presenting 72-bp deletion. This isoform results from a partial deletion of exon 21 due to the use of a cryptic splice site generated by a G to A missense mutation at nucleotide position 2644 in integrin alpha 7 cDNA. This spliced isoform is present in about 12% of the chromosomes studied. We conclude that secondary integrin alpha 7 deficiency is rather common in muscular dystrophy/myopathy of unknown etiology, emphasizing the multiple mechanisms that may modulate integrin function and stability.
authors.affiliation: Neuromuscular Center, Department of Neurological and Psychiatric Sciences, University of Padova, Padova, Italy. elena.pegoraro@unipd.it
authors.forename: Elena
authors.initials: E
authors.lastname: Pegoraro
authors.forename: Fulvio
authors.initials: F
authors.lastname: Cepollaro
authors.forename: Paola
authors.initials: P
authors.lastname: Prandini
authors.forename: Alessandra
authors.initials: A
authors.lastname: Marin
authors.forename: Marina
authors.initials: M
authors.lastname: Fanin
authors.forename: Carlo P
authors.initials: CP
authors.lastname: Trevisan
authors.forename: Abdul Hassib
authors.initials: AH
authors.lastname: El-Messlemani
authors.forename: Guido
authors.initials: G
authors.lastname: Tarone
authors.forename: Eva
authors.initials: E
authors.lastname: Engvall
authors.forename: Eric P
authors.initials: EP
authors.lastname: Hoffman
authors.forename: Corrado
authors.initials: C
authors.lastname: Angelini
mesh_terms: D017398:Alternative Splicing; D001706:Biopsy; D002648:Child; D002675:Child, Preschool; D015536:Down-Regulation; D005260:Female; D005455:Fluorescent Antibody Technique; D006801:Humans; D007223:Infant; D016023:Integrins / Q000172:deficiency / Q000235:genetics / Q000502:physiology*; D008297:Male; D009132:Muscles / Q000473:pathology; D009135:Muscular Diseases / Q000473:pathology / Q000503:physiopathology*; D009136:Muscular Dystrophies / Q000473:pathology / Q000503:physiopathology*; D009154:Mutation; D020125:Mutation, Missense; D020411:Oligonucleotide Array Sequence Analysis; D018807:Polymorphism, Single-Stranded Conformational; D012333:RNA, Messenger / Q000378:metabolism; D015183:Restriction Mapping; D020133:Reverse Transcriptase Polymerase Chain Reaction
chemical_list: D016023:Integrins; D012333:RNA, Messenger; C082908:integrin alpha7beta1