학술논문
Clinicogenetic lessons from 370 patients with autosomal recessive limb-girdle muscular dystrophy.
Document Type
Academic Journal
Author
Winckler PB; Neurology Division, Hospital de Clínicas de Porto Alegre (HCPA), Porto Alegre, Brazil.; Graduate Program in Medicine, Medical Sciences, Universidade Federal do Rio Grande do Sul (UFRGS), Porto Alegre, Brazil.; da Silva AMS; Department of Neurology, Faculdade de Medicina da Universidade de São Paulo (FMUSP), São Paulo, Brazil.; Coimbra-Neto AR; Department of Neurology, Faculdade de Ciências Médicas, Universidade Estadual de Campinas (UNICAMP), Campinas, Brazil.; Graduate Program in Medical Physiopathology, UNICAMP, Campinas, Brazil.; Carvalho E; Rede SARAH de Hospitais de Reabilitação, Belo Horizonte, Brazil.; Cavalcanti EBU; Rede SARAH de Hospitais de Reabilitação, Brasília, Brazil.; Sobreira CFR; Universidade de São Paulo, Ribeirão Preto Medical School, Department of Neurosciences, Ribeirão Preto, Brazil.; Marrone CD; Physiatry Division, Hospital São Lucas da Pontifícia Universidade Católica, Porto Alegre, Brazil.; Clinica Marrone, Porto Alegre, Brazil.; Machado-Costa MC; Escola Bahiana de Medicina e Saúde Pública, Salvador, Brazil.; Carvalho AAS; Centro Universitário Saúde ABC, Santo André, Brazil.; Feio RHF; Hospital Universitário Bettina Ferro de Souza, Universidade Federal do Pará (UFPA), Belém, Brazil.; Rodrigues CL; Neurology Division, Hospital Geral de Fortaleza, Fortaleza, Brazil.; Gonçalves MVM; Universidade da Região de Joinville, Joinville, Brazil.; Tenório RB; Medical Genetics Division, HCPA, Porto Alegre, Brazil.; Mendonça RH; Department of Neurology, Faculdade de Medicina da Universidade de São Paulo (FMUSP), São Paulo, Brazil.; Cotta A; Rede SARAH de Hospitais de Reabilitação, Belo Horizonte, Brazil.; Paim JFO; Rede SARAH de Hospitais de Reabilitação, Belo Horizonte, Brazil.; Costa E Silva C; Rede SARAH de Hospitais de Reabilitação, Brasília, Brazil.; de Aquino Cruz C; Universidade de São Paulo, Ribeirão Preto Medical School, Department of Neurosciences, Ribeirão Preto, Brazil.; Bená MI; Universidade de São Paulo, Ribeirão Preto Medical School, Department of Neurosciences, Ribeirão Preto, Brazil.; Betancur DFA; Physiatry Division, Hospital São Lucas da Pontifícia Universidade Católica, Porto Alegre, Brazil.; El Husny AS; Hospital Universitário Bettina Ferro de Souza, Universidade Federal do Pará (UFPA), Belém, Brazil.; Centro Universitário do Estado do Pará, Belém, Brazil.; de Souza ICN; Hospital Universitário Bettina Ferro de Souza, Universidade Federal do Pará (UFPA), Belém, Brazil.; Duarte RCB; Hospital Ophir Loyola, Belém, Brazil.; Department of Neurology, UFPA, Belém, Brazil.; Reed UC; Department of Neurology, Faculdade de Medicina da Universidade de São Paulo (FMUSP), São Paulo, Brazil.; Chaves MLF; Neurology Division, Hospital de Clínicas de Porto Alegre (HCPA), Porto Alegre, Brazil.; Graduate Program in Medicine, Medical Sciences, Universidade Federal do Rio Grande do Sul (UFRGS), Porto Alegre, Brazil.; Department of Internal Medicine, UFRGS, Porto Alegre, Brazil.; Zanoteli E; Department of Neurology, Faculdade de Medicina da Universidade de São Paulo (FMUSP), São Paulo, Brazil.; França MC Jr; Department of Neurology, Faculdade de Ciências Médicas, Universidade Estadual de Campinas (UNICAMP), Campinas, Brazil.; Graduate Program in Medical Physiopathology, UNICAMP, Campinas, Brazil.; Saute JA; Neurology Division, Hospital de Clínicas de Porto Alegre (HCPA), Porto Alegre, Brazil.; Graduate Program in Medicine, Medical Sciences, Universidade Federal do Rio Grande do Sul (UFRGS), Porto Alegre, Brazil.; Medical Genetics Division, HCPA, Porto Alegre, Brazil.; Department of Internal Medicine, UFRGS, Porto Alegre, Brazil.
Source
Publisher: Munksgaard Country of Publication: Denmark NLM ID: 0253664 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1399-0004 (Electronic) Linking ISSN: 00099163 NLM ISO Abbreviation: Clin Genet Subsets: MEDLINE
Subject
Language
English
Abstract
Limb-girdle muscular dystrophies (LGMD) are a group of genetically heterogeneous disorders characterized by predominantly proximal muscle weakness. We aimed to characterize epidemiological, clinical and molecular data of patients with autosomal recessive LGMD2/LGMD-R in Brazil. A multicenter historical cohort study was performed at 13 centers, in which index cases and their affected relatives' data from consecutive families with genetic or pathological diagnosis of LGMD2/LGMD-R were reviewed from July 2017 to August 2018. Survival curves to major handicap for LGMD2A/LGMD-R1-calpain3-related, LGMD2B/LGMD-R2-dysferlin-related and sarcoglycanopathies were built and progressions according to sex and genotype were estimated. In 370 patients (305 families) with LGMD2/LGMD-R, most frequent subtypes were LGMD2A/LGMD-R1-calpain3-related and LGMD2B/LGMD-R2-dysferlin-related, each representing around 30% of families. Sarcoglycanopathies were the most frequent childhood-onset subtype, representing 21% of families. Five percent of families had LGMD2G/LGMD-R7-telethonin-related, an ultra-rare subtype worldwide. Females with LGMD2B/LGMD-R2-dysferlin-related had less severe progression to handicap than males and LGMD2A/LGMD-R1-calpain3-related patients with truncating variants had earlier disease onset and more severe progression to handicap than patients without truncating variants. We have provided paramount epidemiological data of LGMD2/LGMD-R in Brazil that might help on differential diagnosis, better patient care and guiding future collaborative clinical trials and natural history studies in the field.
(© 2019 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)
(© 2019 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)