Frontiers in Genetics (Mar 2023)

LMNA-related muscular dystrophy: Identification of variants in alternative genes and personalized clinical translation

  • Sergi Cesar,
  • Sergi Cesar,
  • Sergi Cesar,
  • Monica Coll,
  • Monica Coll,
  • Victoria Fiol,
  • Victoria Fiol,
  • Victoria Fiol,
  • Anna Fernandez-Falgueras,
  • Anna Fernandez-Falgueras,
  • Jose Cruzalegui,
  • Jose Cruzalegui,
  • Jose Cruzalegui,
  • Anna Iglesias,
  • Anna Iglesias,
  • Isaac Moll,
  • Isaac Moll,
  • Isaac Moll,
  • Alexandra Perez-Serra,
  • Alexandra Perez-Serra,
  • Estefanía Martínez-Barrios,
  • Estefanía Martínez-Barrios,
  • Estefanía Martínez-Barrios,
  • Carles Ferrer-Costa,
  • Carles Ferrer-Costa,
  • Bernat del Olmo,
  • Bernat del Olmo,
  • Marta Puigmulè,
  • Marta Puigmulè,
  • Marta Puigmulè,
  • Mireia Alcalde,
  • Mireia Alcalde,
  • Laura Lopez,
  • Laura Lopez,
  • Ferran Pico,
  • Ferran Pico,
  • Rubén Berrueco,
  • Josep Brugada,
  • Josep Brugada,
  • Josep Brugada,
  • Josep Brugada,
  • Josep Brugada,
  • Irene Zschaeck,
  • Irene Zschaeck,
  • Irene Zschaeck,
  • Irene Zschaeck,
  • Irene Zschaeck,
  • Daniel Natera-de Benito,
  • Daniel Natera-de Benito,
  • Laura Carrera-García,
  • Laura Carrera-García,
  • Jessica Exposito-Escudero,
  • Jessica Exposito-Escudero,
  • Carlos Ortez,
  • Carlos Ortez,
  • Andrés Nascimento,
  • Andrés Nascimento,
  • Andrés Nascimento,
  • Ramon Brugada,
  • Ramon Brugada,
  • Ramon Brugada,
  • Ramon Brugada,
  • Georgia Sarquella-Brugada,
  • Georgia Sarquella-Brugada,
  • Georgia Sarquella-Brugada,
  • Georgia Sarquella-Brugada,
  • Oscar Campuzano,
  • Oscar Campuzano,
  • Oscar Campuzano

DOI
https://doi.org/10.3389/fgene.2023.1135438
Journal volume & issue
Vol. 14

Abstract

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Background: Laminopathies are caused by rare alterations in LMNA, leading to a wide clinical spectrum. Though muscular dystrophy begins at early ages, disease progression is different in each patient. We investigated variability in laminopathy phenotypes by performing a targeted genetic analysis of patients diagnosed with LMNA-related muscular dystrophy to identify rare variants in alternative genes, thereby explaining phenotypic differences.Methods: We analyzed 105 genes associated with muscular diseases by targeted sequencing in 26 pediatric patients of different countries, diagnosed with any LMNA-related muscular dystrophy. Family members were also clinically assessed and genetically analyzed.Results: All patients carried a pathogenic rare variant in LMNA. Clinical diagnoses included Emery-Dreifuss muscular dystrophy (EDMD, 13 patients), LMNA-related congenital muscular dystrophy (L-CMD, 11 patients), and limb-girdle muscular dystrophy 1B (LGMD1B, 2 patients). In 9 patients, 10 additional rare genetic variants were identified in 8 genes other than LMNA. Genotype-phenotype correlation showed additional deleterious rare variants in five of the nine patients (3 L-CMD and 2 EDMD) with severe phenotypes.Conclusion: Analysis f known genes related to muscular diseases in close correlation with personalized clinical assessments may help identify additional rare variants of LMNA potentially associated with early onset or most severe disease progression.

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