Affiliations: [a] APHP, Reference Center for Neuromuscular Disorders, Institut de Myologie, Pitié-Salpêtrière Hospital, Paris, France
| [b] INSERM, Institut de Myologie, Centre de Recherche en Myologie, Sorbonne Université, Paris, France
| [c] AP-HP, Centre de Génétique Moléculaire et Chromosomique, UF Cardiomyogénétique et Myogénétique Moléculaire et Cellulaire, Pitié-Salpêtrière Hospital, Paris, France
| [d]
Neuromuscular Morphology Unit, Institut de Myologie, APHP, Pitié-Salpêtrière Hospital, Paris, France
| [e] Département de génétique, Hôpital Universitaire Robert Debré, Paris, France
Correspondence:
[*]
Correspondence to: Dr Tanya Stojkovic, Centre de Référence des maladies neuromusculaires Nord / Est / Ile-de-France, Groupe Hospitalier Pitié-Salpêtrière, 47-83 boulevard de l’Hôpital, 75651 Paris Cedex 13, France. E-mail: [email protected].
Abstract: We report three siblings from a non-consanguineous family presenting with contractural limb-girdle phenotype with intrafamilial variability. Muscle MRI showed posterior thigh and quadriceps involvement with a sandwich-like sign. Whole-exome sequencing identified two compound heterozygous missense TTN variants and one heterozygous LAMA2 variant. Brain MRI performed because of concentration difficulties in one of the siblings evidenced white-matter abnormalities, subsequently found in the others. The genetic analysis was re-oriented, revealing a novel pathogenic intronic LAMA2 variant which confirmed the LAMA2-RD diagnosis. This work highlights the importance of a thorough clinical phenotyping and the importance of brain imaging, in order to orientate and interpret the genetic analysis.
Keywords: Limb-girdle muscular dystrophy, LAMA2, white matter, brain MRI, laminin-211
