Genetic profile of Brazilian patients with LAMA2-related dystrophies.

Autor: Camelo CG; Department of Neurology, Faculdade de Medicina da Universidade de São Paulo (FMUSP), São Paulo, SP, Brazil., Moreno CAM; Department of Neurology, Faculdade de Medicina da Universidade de São Paulo (FMUSP), São Paulo, SP, Brazil., Artilheiro MDC; Department of Neurology, Faculdade de Medicina da Universidade de São Paulo (FMUSP), São Paulo, SP, Brazil., Fonseca ATQM; Department of Neurology, Faculdade de Medicina da Universidade de São Paulo (FMUSP), São Paulo, SP, Brazil., Gurgel Gianetti J; Department of Pediatrics, Faculty of Medicine, Universidade Federal de Minas Gerais, Belo Horizonte, Brazil., Barbosa AV; Department of Pediatric Neurology, Fundação Hospitalar do Estado de Minas Gerais, Belo Horizonte, Brazil., Donis KC; Medical Genetics Division and Neurology Division, Hospital de Clínicas de Porto Alegre, Porto Alegre, Brazil., Saute JAM; Medical Genetics Division and Neurology Division, Hospital de Clínicas de Porto Alegre, Porto Alegre, Brazil., Pessoa A; Children's Hospital Albert Sabin, Fortaleza, Brazil., Van der Linden H Jr; Rehabilitation Center Dr. Henrique Santillo, Goiânia, Brazil.; Neurology Institute of Goiânia, Goiânia, Brazil., Gonçalves ARA; Centro de Genética Médica Jacinto Magalhães, Centro Hospitalar Universitário de Santo António (CHUdSA), Porto, Portugal.; UMIB-Unit for Multidisciplinary Research in Biomedicine, ICBAS-School of Medicine and Biomedical Sciences, University of Porto, Porto, Portugal.; ITR-Laboratory for Integrative and Translational Research in Population Health, Porto, Portugal., Kulikowski LD; Department of Neurology, Faculdade de Medicina da Universidade de São Paulo (FMUSP), São Paulo, SP, Brazil., Kok F; Department of Neurology, Faculdade de Medicina da Universidade de São Paulo (FMUSP), São Paulo, SP, Brazil., Zanoteli E; Department of Neurology, Faculdade de Medicina da Universidade de São Paulo (FMUSP), São Paulo, SP, Brazil.
Jazyk: angličtina
Zdroj: Clinical genetics [Clin Genet] 2024 Sep; Vol. 106 (3), pp. 305-314. Date of Electronic Publication: 2024 May 15.
DOI: 10.1111/cge.14538
Abstrakt: LAMA2-related dystrophies (LAMA2-RD) constitute a rare neuromuscular disorder with a broad spectrum of phenotypic severity. Our understanding of the genotype-phenotype correlations in this condition remains incomplete, and reliable clinical data for clinical trial readiness is limited. In this retrospective study, we reviewed the genetic data and medical records of 114 LAMA2-RD patients enrolled at seven research centers in Brazil. We identified 58 different pathogenic variants, including 21 novel ones. Six variants were more prevalent and were present in 81.5% of the patients. Notably, the c.1255del, c.2049_2050del, c.3976 C>T, c.5234+1G>A, and c.4739dup variants were found in patients unable to walk and without cortical malformation. In contrast, the c.2461A>C variant was present in patients who could walk unassisted. Among ambulatory patients, missense variants were more prevalent (p < 0.0001). Although no specific hotspot regions existed in the LAMA2, 51% of point mutations were in the LN domain, and 88% of the missense variants were found within this domain. Functional analysis was performed in one intronic variant (c.4960-17C>A) and revealed an out-of-frame transcript, indicating that the variant creates a cryptic splicing site (AG). Our study has shed light on crucial phenotype-genotype correlations and provided valuable insights, particularly regarding the Latin American population.
(© 2024 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)
Databáze: MEDLINE
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