title: Clinical and myopathological evaluation of early- and late-onset subtypes of myofibrillar myopathy.
abstract: Myofibrillar myopathies (MFM) are a group of disorders associated with mutations in DES, CRYAB, MYOT, ZASP, FLNC, or BAG3 genes and characterized by disintegration of myofibrils and accumulation of degradation products into intracellular inclusions. We retrospectively evaluated 53 MFM patients from 35 Spanish families. Studies included neurologic exam, muscle imaging, light and electron microscopic analysis of muscle biopsy, respiratory function testing and cardiologic work-up. Search for pathogenic mutations was accomplished by sequencing of coding regions of the six genes known to cause MFM. Mutations in MYOT were the predominant cause of MFM in Spain affecting 18 of 35 families, followed by DES in 11 and ZASP in 3; in 3 families the cause of MFM remains undetermined. Comparative analysis of DES, MYOT and ZASP associated phenotypes demonstrates substantial phenotypic distinctions that should be considered in studies of disease pathogenesis, for optimization of subtype-specific treatments and management, and directing molecular analysis.
authors.affiliation: Institute of Neuropathology, Department of Pathology, IDIBELL-Hospital de Bellvitge, Hospitalet de Llobregat, Barcelona, Spain. 25169mop@comb.cat
authors.forename: Montse
authors.initials: M
authors.lastname: Olivé
authors.forename: Zagaa
authors.initials: Z
authors.lastname: Odgerel
authors.forename: Amaia
authors.initials: A
authors.lastname: Martínez
authors.forename: Juan José
authors.initials: JJ
authors.lastname: Poza
authors.forename: Federico García
authors.initials: FG
authors.lastname: Bragado
authors.forename: Ramón J
authors.initials: RJ
authors.lastname: Zabalza
authors.forename: Ivonne
authors.initials: I
authors.lastname: Jericó
authors.forename: Laura
authors.initials: L
authors.lastname: Gonzalez-Mera
authors.forename: Alexey
authors.initials: A
authors.lastname: Shatunov
authors.forename: Hee Suk
authors.initials: HS
authors.lastname: Lee
authors.forename: Judith
authors.initials: J
authors.lastname: Armstrong
authors.forename: Elías
authors.initials: E
authors.lastname: Maraví
authors.forename: Maria Ramos
authors.initials: MR
authors.lastname: Arroyo
authors.forename: Jordi
authors.initials: J
authors.lastname: Pascual-Calvet
authors.forename: Carmen
authors.initials: C
authors.lastname: Navarro
authors.forename: Carmen
authors.initials: C
authors.lastname: Paradas
authors.forename: Mariano
authors.initials: M
authors.lastname: Huerta
authors.forename: Fabian
authors.initials: F
authors.lastname: Marquez
authors.forename: Eduardo Gutierrez-
authors.initials: EG
authors.lastname: Rivas
authors.forename: Adolf
authors.initials: A
authors.lastname: Pou
authors.forename: Isidre
authors.initials: I
authors.lastname: Ferrer
authors.forename: Lev G
authors.initials: LG
authors.lastname: Goldfarb
mesh_terms: D048868:Adaptor Proteins, Signal Transducing / Q000235:genetics; D000293:Adolescent; D000328:Adult; D017668:Age of Onset; D000368:Aged; D001706:Biopsy; D064211:Connectin; D003598:Cytoskeletal Proteins / Q000235:genetics; D003893:Desmin / Q000235:genetics; D005260:Female; D006801:Humans; D060588:LIM Domain Proteins / Q000235:genetics; D008279:Magnetic Resonance Imaging; D008297:Male; D008840:Microfilament Proteins; D008875:Middle Aged; D009124:Muscle Proteins / Q000235:genetics; D009135:Muscular Diseases / Q000145:classification* / Q000235:genetics / Q000473:pathology*; D009154:Mutation / Q000235:genetics; D009210:Myofibrils / Q000473:pathology*; D010641:Phenotype; D012189:Retrospective Studies; D013030:Spain; D055815:Young Adult
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D064211:Connectin; D003598:Cytoskeletal Proteins; D003893:Desmin; C120696:LDB3 protein, human; D060588:LIM Domain Proteins; C577290:MYOT protein, human; D008840:Microfilament Proteins; D009124:Muscle Proteins