Clinicogenetic lessons from 370 patients with autosomal recessive limb-girdle muscular dystrophy.

Autor: 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.
Jazyk: angličtina
Zdroj: Clinical genetics [Clin Genet] 2019 Oct; Vol. 96 (4), pp. 341-353. Date of Electronic Publication: 2019 Jul 15.
DOI: 10.1111/cge.13597
Abstrakt: 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.)
Databáze: MEDLINE
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