Details

Autor(en) / Beteiligte

• Winckler, Pablo B.
• Silva, André M.S.
• Coimbra‐Neto, Antônio R.
• Carvalho, Elmano
• Cavalcanti, Eduardo B.U.
• Sobreira, Cláudia F.R.
• Marrone, Carlo D.
• Machado‐Costa, Marcela C.
• Carvalho, Alzira A.S.
• Feio, Raimunda H.F.
• Rodrigues, Cleonísio L.
• Gonçalves, Marcus V.M.
• Tenório, Renata B.
• Mendonça, Rodrigo H.
• Cotta, Ana
• Paim, Júlia F.O.
• Costa e Silva, Cynthia
• Aquino Cruz, Camila
• Bená, Marjory I.
• Betancur, Daniel F.A.
• El Husny, Antonette S.
• Souza, Isabel C.N.
• Duarte, Regina C.B.
• Reed, Umbertina C.
• Chaves, Márcia L.F.
• Zanoteli, Edmar
• França, Marcondes C.
• Saute, Jonas A.

Titel

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

Ist Teil von

• Clinical genetics, 2019-10, Vol.96 (4), p.341-353

Ort / Verlag

Oxford, UK: Blackwell Publishing Ltd

Erscheinungsjahr

2019

Quelle

Wiley Online Library Journals Frontfile Complete

Beschreibungen/Notizen

• 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.