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Clin Genet ; 96(4): 341-353, 2019 10.
Artículo en Inglés | MEDLINE | ID: mdl-31268554

RESUMEN

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.


Asunto(s)
Genes Recesivos , Estudios de Asociación Genética , Predisposición Genética a la Enfermedad , Distrofia Muscular de Cinturas/diagnóstico , Distrofia Muscular de Cinturas/genética , Edad de Inicio , Alelos , Biomarcadores , Brasil , Progresión de la Enfermedad , Femenino , Frecuencia de los Genes , Estudios de Asociación Genética/métodos , Genotipo , Geografía Médica , Humanos , Masculino , Debilidad Muscular , Distrofia Muscular de Cinturas/epidemiología , Fenotipo , Factores Sexuales
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