Case report: Clinical and molecular characterization of two siblings affected by Brody myopathy

Frontiers in Neurology

Neurology

Martina Rimoldi¹  Dario Ronchi¹  Sara Antognozzi²  Serena Pagliarani²  Stefania Corti³  Daniele Velardo⁴  Giacomo Pietro Comi⁵  Sergio Barbieri⁶  Filippo Cogiamanian⁶ 

[1] Dino Ferrari Center, Department of Pathophysiology and Transplantation, University of Milan, Milan, Italy;Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico, Neurology Unit, Milan, Italy;Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico, Neurology Unit, Milan, Italy;Dino Ferrari Center, Department of Pathophysiology and Transplantation, University of Milan, Milan, Italy;Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico, Neuromuscular and Rare Disease Unit, Milan, Italy;Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico, Neuromuscular and Rare Disease Unit, Milan, Italy;Dino Ferrari Center, Department of Pathophysiology and Transplantation, University of Milan, Milan, Italy;Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico, Neurophysiology Unit, Milan, Italy;

关键词: Brody myopathy;    SERCA1;    ATP2A1;    WES;    neuromuscular disorder;   

DOI  :  10.3389/fneur.2023.1170071

 received in 2023-02-20, accepted in 2023-05-16,  发布年份 2023

来源: Frontiers

【 摘 要 】

Exercise-induced muscle stiffness is the hallmark of Brody disease, an autosomal recessive myopathy due to biallelic pathogenic variants in ATP2A1, encoding the sarcoplasmic/endoplasmic reticulum Ca2+ ATPase SERCA1. About 40 patients have been reported so far. Our knowledge about the natural history of this disorder, genotype–phenotype correlations and the effect of symptomatic treatment is partial. This results in incomplete recognition and underdiagnosis of the disease. Here, we report the clinical, instrumental, and molecular features of two siblings presenting childhood-onset exercise-induced muscle stiffness without pain. Both the probands display difficulty in climbing stairs and running, frequent falls, delayed muscle relaxation after exertion. Cold temperatures worsen these symptoms. No myotonic discharges were observed at electromyography. Whole Exome Sequencing analysis in the probands revealed the presence of two ATP2A1 variants: the previously reported frameshift microdeletion c.2464delC and the likely pathogenic novel splice-site variant c.324 + 1G > A, whose detrimental effect was demonstrated in ATP2A1 transcript analysis. The bi-allelic inheritance was verified by Sanger sequencing in the unaffected parents. This study expands the molecular defects associated with Brody myopathy.

【 授权许可】

Unknown   
Copyright © 2023 Velardo, Antognozzi, Rimoldi, Pagliarani, Cogiamanian, Barbieri, Corti, Comi and Ronchi.