Two Moroccan Families with Emery-Dreifuss Muscular Dystrophy and Report of a Novel LMNA Pathogenic Variant

Abstract

Background: Emery-Dreifuss muscular dystrophy (EDMD) is a neuromuscular disorder characterized by muscle weakness and atrophy associated with early tendon retractions and late cardiomyopathy. Among several genes, EMD and LMNA are the major ones (55%). Due to intra- and inter-familial heterogeneity, only NGS allows to confirm with certainty EDMD by identifying the mutation in the causal gene.

Case presentation: We report clinical and molecular data of two unrelated Moroccan patients with EDMD in whom we identified a deleterious hemizygous splicing variant NM_000117.3(EMD): c.399 + 1G>T and a novel frameshift variant NM_170707.4(LMNA): c.1549_1550delCA, respectively. Carrier status of the EMD variant was investigated in several relatives at risk.

Conclusion: We emphasize the importance of NGS as a powerful genetic tool in EDMD for accurate molecular diagnosis, effective clinical management of patients, and appropriate genetic counseling of families.

Keywords: EMD; Emery-Dreifuss muscular dystrophy; LMNA; NGS.

Fig. 1.

Pedigrees of the families affected by EDMD. Affected individuals are shaded. Arrows indicate individuals in whom blood was analyzed.

Fig. 2.

Molecular results of the two studied families. a Hemizygous, heterozygous, and wild-type profile of NM_000117.3(EMD): c.399 + 1G>T variant by DNA sequencing. b Skipping of exon 4 of EMD gene in patient (FI: V2) showed by cDNA sequencing. c The result of DNA Sanger sequencing of proband FII: III-1 showing the c.1549_1550delCA variant, resulting in a 2-base deletion and a frameshift p.Gln517Glufs*34 in LMNA gene.