Intrafamilial phenotypic heterogeneity related to a new DMD splice site variant

Autor(es)

Coimbra Neto, Antonio Rodrigues ^[1] ; de Carvalho, Samara Camacari ^{[2, 3]} ; Leoni, Tauana Bernardes ^[1] ; Iwabe, Cristina ^[1] ; Araujo Costa Silva, Thiago Quinaglia ^[4] ; Coelho-Filho, Otavio Rizzi ^[4] ; Marques, Maria Julia ^[2] ; Nucci, Anamarli ^[1] ; Franca Jr, Marcondes Cavalcante

Afiliação do(s) autor(es)

^[1] Univ Campinas UNICAMP, Dept Neurol, Sch Med Sci, 126 Cidade Univ Zeferino Vaz, BR-13083887 Campinas, SP - Brazil

^[2] Univ Campinas UNICAMP, Inst Biol, Dept Struct & Funct Biol, Campinas, SP - Brazil

^[3] Univ Ctr Herminio Ometto Fdn, Postgrad Program Biomed Sci, Araras, SP - Brazil

^[4] Univ Campinas UNICAMP, Sch Med Sci, Dept Internal Med, Discipline Cardiol, Campinas, SP - Brazil

• Tipo de documento: Artigo Científico
• Fonte: Neuromuscular Disorders; v. 31, n. 8, p. 788-797, AUG 2021.
• Citações Web of Science: 0

Resumo

Dystrophinopathies are a group of X-linked neuromuscular disorders that result from pathogenic variants in the DMD gene. Their pathophysiological substrate is the defective expression of dystrophin in many tissues. While patients from the same pedigree usually present similar dystrophin expression and clinical course, the extent of cardiac and skeletal muscle involvement may not correlate in the same individual. We identified a new splice site variant c.2803+5G>C (NM\_004006) ClinVar VCV000803902, located in intron 22 of DMD in a Brazilian family that present a broad phenotypic and histological heterogeneity. One of the subjects had a typical Duchenne muscular dystrophy (DMD) phenotype, whereas the others had Becker muscular dystrophy (BMD). Cardiac involvement was remarkable in some of the BMD patients, but not in the DMD patient. Western blot analysis of skeletal muscle revealed much lower levels of calsequestrin in the most severely affected patient compared to his brother, whose phenotype is BMD, highlighting the potential role of proteins involved in skeletal muscle calcium homeostasis in differential degrees of dystrophinopathies. (C) 2021 Elsevier B.V. All rights reserved. (AU)

• Processo FAPESP: 13/07559-3 - Instituto Brasileiro de Neurociência e Neurotecnologia - BRAINN
• Beneficiário: Fernando Cendes
• Modalidade de apoio: Auxílio à Pesquisa - Centros de Pesquisa, Inovação e Difusão - CEPIDs