Clinical and molecular characterization of limb-girdle muscular dystrophy 2G/R7 in a large cohort of Brazilian patients.
Tobias GaviraghiEduardo B U CavalcantiPaulo LorenzoniAna CottaPaulo V S de SouzaAndré D de OliveiraMaria T de MoraesMarcos V O MarquesKarina C DonisPablo B WincklerCynthia Costa E SilvaWladimir B V R PintoCláudia S K KayRenata D DucciPaula R V P RodriguesOtto Jesus Hernández FustesAndré M S da SilvaEdmar ZanoteliMarcondes Cavalcante de França JuniorCláudia F R SobreiraAcary S B OliveiraElmano H T CarvalhoRosana H ScolaAlzira A S CarvalhoJonas Alex Morales SautePublished in: Clinical genetics (2024)
Limb-girdle muscular dystrophy type 2G/R7 (LGMD2G/R7) is an ultra-rare condition initially identified within the Brazilian population. We aimed to expand clinical and genetic information about this disease, including its worldwide distribution. A multicenter historical cohort study was performed at 13 centers in Brazil in which data from index cases and their affected relatives from consecutive families with LGMD2G/R7 were reviewed from July 2017 to August 2023. Additionally, a systematic literature review was conducted to identify case reports and series of the disease worldwide. Forty-one LGMD2G/R7 cases were described in the Brazilian cohort, being all subjects homozygous for the c.157C>T/(p.Gln53*) variant in TCAP. Survival curves showed that the median disease duration before individuals required walking aids was 21 years. Notably, women exhibited a slower disease progression, requiring walking aids 13 years later than men. LGMD2G/R7 was frequently reported not only in Brazil but also in China and Bulgaria, with 119 cases identified globally, with possible founder effects in the Brazilian, Eastern European, and Asian populations. These findings are pivotal in raising awareness of LGMD2G/R7, understanding its progression, and identifying potential modifiers. This can significantly contribute to the development of future natural history studies and clinical trials for this disease.
Keyphrases
- muscular dystrophy
- clinical trial
- duchenne muscular dystrophy
- end stage renal disease
- healthcare
- ejection fraction
- south africa
- chronic kidney disease
- dna methylation
- high resolution
- health information
- randomized controlled trial
- artificial intelligence
- electronic health record
- case report
- machine learning
- big data
- mass spectrometry
- middle aged
- patient reported outcomes
- data analysis
- case control
- patient reported