title: Laminin α2 Deficiency-Related Muscular Dystrophy Mimicking Emery-Dreifuss and Collagen VI related Diseases.
abstract: BACKGROUND
  Laminin α2 deficient congenital muscular dystrophy, caused by mutations in the LAMA2 gene, is characterized by early muscle weakness associated with abnormal white matter signal on cerebral MRI.
  
  
  OBJECTIVE
  To report on 4 patients with LAMA2 gene mutations whose original clinical features complicated the diagnosis strategy.
  
  
  METHODS
  Clinical, electrophysiological, muscle imaging and histopathological data were retrospectively collected from all patients. DNA samples were analysed by next-generation sequencing or direct gene sequencing. Laminin α2 was analysed by western-blot and immunohistochemistry.
  
  
  RESULTS
  The four patients achieved independent walking. All had proximal muscle weakness with scapular winging and prominent joint contractures without peripheral neuropathy. During follow-up, two patients suffered from refractory epilepsy associated with brain leukoencephalopathy in one, polymicrogyria and lissencephaly without white matter changes in the other. In two patients, the distribution of fatty infiltration resembles that of collagen-VI related myopathies. Dilated cardiomyopathy contstartabstractwith conduction defects, suggestive of Emery-Dreifuss myopathy, emerged in two of them within the 4th decade. Molecular diagnosis remained elusive for many years. Finally, targeted capture-DNA sequencing unveiled the involvement of the LAMA2 gene in two families, and led us to further identify LAMA2 mutations in the remaining family using Sanger sequencing.
  
  
  CONCLUSIONS
  This report extends the clinical and radiological features of partial Laminin α2 deficiency since patients showed atypical manifestations including dilated cardiomyopathy with conduction defects in 2, epilepsy in 2, one of whom also had sole cortical brain abnormalities. Importantly, clinical findings and muscle imaging initially pointed to collagen-VI related disorders and Emery-Dreifuss muscular dystrophy.
authors.affiliation: Sorbonne Universités,UPMCUniv Paris 06, INSERM UMRS974, CNRS FRE3617, Center of Research in Myology, F-75013 Paris, France.|Institut de Myologie, F-75013, Paris, France.
authors.forename: Isabelle
authors.initials: I
authors.lastname: Nelson
authors.affiliation: Sorbonne Universités,UPMCUniv Paris 06, INSERM UMRS974, CNRS FRE3617, Center of Research in Myology, F-75013 Paris, France.|Institut de Myologie, F-75013, Paris, France.
authors.forename: Tanya
authors.initials: T
authors.lastname: Stojkovic
authors.affiliation: Sorbonne Universités,UPMCUniv Paris 06, INSERM UMRS974, CNRS FRE3617, Center of Research in Myology, F-75013 Paris, France.|Institut de Myologie, F-75013, Paris, France.
authors.forename: Valérie
authors.initials: V
authors.lastname: Allamand
authors.affiliation: Sorbonne Universités,UPMCUniv Paris 06, INSERM UMRS974, CNRS FRE3617, Center of Research in Myology, F-75013 Paris, France.|AP-HP, Groupe Hospitalier Cochin-Broca-Hôtel Dieu, Laboratoire de biochimie et génétique moléculaire, Paris, France.
authors.forename: France
authors.initials: F
authors.lastname: Leturcq
authors.affiliation: Institut de Myologie, F-75013, Paris, France.|AP-HP, Groupe Hospitalier La Pitié-Salpêtrière, Centre de référence des maladies neuromusculaires Paris Est, F-75013, Paris, France.
authors.forename: Henri-Marc
authors.initials: HM
authors.lastname: Bécane
authors.affiliation: Service de Cardiologie, Hôpital Trousseau, CHU Tours, Tours, France.
authors.forename: Dominique
authors.initials: D
authors.lastname: Babuty
authors.affiliation: Service de Génétique, Hôpital Bretonneau, CHU Tours, Tours, France.
authors.forename: Annick
authors.initials: A
authors.lastname: Toutain
authors.affiliation: INSERM UMR S910, AP-HM, service de génétique médicale, Aix Marseille Université, Marseille, France.
authors.forename: Christophe
authors.initials: C
authors.lastname: Béroud
authors.affiliation: AP-HP, Groupe Hospitalier La Pitié-Salpôtrière, U.F. Cardiogénétique et Myogénétique, Service de Biochimie Métabolique, F-75013, Paris, France.
authors.forename: Pascale
authors.initials: P
authors.lastname: Richard
authors.affiliation: Sorbonne Universités,UPMCUniv Paris 06, INSERM UMRS974, CNRS FRE3617, Center of Research in Myology, F-75013 Paris, France.|Institut de Myologie, F-75013, Paris, France.|AP-HP, Groupe Hospitalier La Pitié-Salpêtrière, Centre de référence des maladies neuromusculaires Paris Est, F-75013, Paris, France.|Unité de morphologieneuromusculaire, Institut de Myologie, Groupe Hospitalier Universitaire La Pitié-Salpêtrière, F-75013, Paris, France.
authors.forename: Norma B
authors.initials: NB
authors.lastname: Romero
authors.affiliation: Institut de Myologie, F-75013, Paris, France.|AP-HP, Groupe Hospitalier La Pitié-Salpêtrière, Centre de référence des maladies neuromusculaires Paris Est, F-75013, Paris, France.
authors.forename: Bruno
authors.initials: B
authors.lastname: Eymard
authors.affiliation: Sorbonne Universités,UPMCUniv Paris 06, INSERM UMRS974, CNRS FRE3617, Center of Research in Myology, F-75013 Paris, France.|Institut de Myologie, F-75013, Paris, France.|AP-HP, Groupe Hospitalier La Pitié-Salpêtrière, Centre de référence des maladies neuromusculaires Paris Est, F-75013, Paris, France.
authors.forename: Rabah
authors.initials: R
authors.lastname: Ben Yaou
authors.affiliation: Sorbonne Universités,UPMCUniv Paris 06, INSERM UMRS974, CNRS FRE3617, Center of Research in Myology, F-75013 Paris, France.|Institut de Myologie, F-75013, Paris, France.
authors.forename: Gisèle
authors.initials: G
authors.lastname: Bonne
keywords: Emery-Dreifuss muscular dystrophy; LAMA2; Laminin alpha 2; collagen VI-related myopathy; congenital muscular dystrophy; dilated cardiomyopathy