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.

1.
Mah
JK
,
Korngut
L
,
Fiest
KM
,
Dykeman
J
,
Day
LJ
,
Pringsheim
T
, et al
.
A systematic review and meta-analysis on the epidemiology of the muscular dystrophies
.
Can J Neurol Sci
.
2016
;
43
(
1
):
163
77
.
2.
Díaz-Manera
J
,
Alejaldre
A
,
González
L
,
Olivé
M
,
Gómez-Andrés
D
,
Muelas
N
, et al
.
Muscle imaging in muscle dystrophies produced by mutations in the EMD and LMNA genes
.
Neuromuscul Disord
.
2016
;
26
(
1
):
33
40
.
3.
Wu
L
,
Xiang
B
,
Zhang
H
,
He
X
,
Shih
C
,
Chen
X
, et al
.
Three novel recessive mutations in LAMA2, SYNE1, and TTN are identified in a single case with congenital muscular dystrophy
.
Neuromuscul Disord
.
2017
;
27
(
11
):
1018
22
.
4.
Koch
AJ
,
Holaska
JM
.
Emerin in health and disease
.
Semin Cell Dev Biol
.
2014
;
29
:
95
106
.
5.
Emery
AE
,
Dreifuss
FE
.
Unusual type of benign x-linked muscular dystrophy
.
J Neurol Neurosurg Psychiatry
.
1966
;
29
(
4
):
338
42
.
6.
Bonne
G
,
Di Barletta
MR
,
Varnous
S
,
Bécane
HM
,
Hammouda
EH
,
Merlini
L
, et al
.
Mutations in the gene encoding lamin A/C cause autosomal dominant Emery-Dreifuss muscular dystrophy
.
Nat Genet
.
1999
;
21
(
3
):
285
8
.
7.
Raffaele Di Barletta
M
,
Ricci
E
,
Galluzzi
G
,
Tonali
P
,
Mora
M
,
Morandi
L
, et al
.
Different mutations in the LMNA gene cause autosomal dominant and autosomal recessive emery-dreifuss muscular dystrophy
.
Am J Hum Genet
.
2000
;
66
(
4
):
1407
12
.
8.
Brown
CA
,
Scharner
J
,
Felice
K
,
Meriggioli
MN
,
Tarnopolsky
M
,
Bower
M
, et al
.
Novel and recurrent EMD mutations in patients with Emery–Dreifuss muscular dystrophy, identify exon 2 as a mutation hot spot
.
J Hum Genet
.
2011
;
56
(
8
):
589
94
.
9.
Heller
SA
,
Shih
R
,
Kalra
R
,
Kang
PB
.
Emery-Dreifuss muscular dystrophy
.
Muscle Nerve
.
2020
;
61
(
4
):
436
48
.
10.
Bonne
G
,
Mercuri
E
,
Muchir
A
,
Urtizberea
A
,
Bécane
HM
,
Recan
D
, et al
.
Clinical and molecular genetic spectrum of autosomal dominant Emery-Dreifuss muscular dystrophy due to mutations of the Lamin A/C gene
.
Ann Neurol
.
2000
;
48
(
2
):
170
80
.
11.
Vytopil
M
,
Benedetti
S
,
Ricci
E
,
Galluzzi
G
,
Dello Russo
A
,
Merlini
L
, et al
.
Mutation analysis of the Lamin A/C gene (LMNA) among patients with different cardiomuscular phenotypes
.
J Med Genet
.
2003
;
40
(
12
):
132e-132
.
12.
Yates
JR
,
Bagshaw
J
,
Aksmanovic
VM
,
Coomber
E
,
McMahon
R
,
Whittaker
JL
, et al
.
Genotype-phenotype analysis in X-linked Emery-Dreifuss muscular dystrophy and identification of a missense mutation associated with a milder phenotype
.
Neuromuscul Disord
.
1999
;
9
(
3
):
159
65
.
13.
Bonne
G
,
Quijano-Roy
S
.
Emery–Dreifuss muscular dystrophy, laminopathies, and other nuclear envelopathies
.
Handbook of clinical neurology [internet]
.
Elsevier
;
2013
. [cité 27 févr 2024]. pp.
1367–76
. Disponible sur: https://linkinghub.elsevier.com/retrieve/pii/B9780444595652000071.
14.
Hausmanowa-Petrusewicz
I
,
Madej-Pilarczyk
A
,
Marchel
M
,
Opolski
G
.
Emery-Dreifuss dystrophy: a 4-year follow-up on a laminopathy of special interest
.
Neurol Neurochir Pol
.
2009
;
43
(
5
):
415
20
.
15.
Manilal
S
,
Recan
D
,
Sewry
CA
,
Hoeltzenbein
M
,
Llense
S
,
Leturcq
F
, et al
.
Mutations in Emery-Dreifuss muscular dystrophy and their effects on emerin protein expression
.
Hum Mol Genet
.
1998
;
7
(
5
):
855
64
.
16.
Brown
CA
,
Lanning
RW
,
McKinney
KQ
,
Salvino
AR
,
Cherniske
E
,
Crowe
CA
, et al
.
Novel and recurrent mutations in lamin A/C in patients with Emery-Dreifuss muscular dystrophy
.
Am J Med Genet
.
2001
;
102
(
4
):
359
67
.
17.
Carboni
N
,
Porcu
M
,
Mura
M
,
Cocco
E
,
Marrosu
G
,
Maioli
MA
, et al
.
Evolution of the phenotype in a family with an LMNA gene mutation presenting with isolated cardiac involvement
.
Muscle Nerve
.
2010
;
41
(
1
):
85
91
.
18.
Benedetti
S
,
Menditto
I
,
Degano
M
,
Rodolico
C
,
Merlini
L
,
D’Amico
A
, et al
.
Phenotypic clustering of Lamin A/C mutations in neuromuscular patients
.
Neurology
.
2007
;
69
(
12
):
1285
92
.
19.
Scharner
J
,
Brown
CA
,
Bower
M
,
Iannaccone
ST
,
Khatri
IA
,
Escolar
D
, et al
.
Novel LMNA mutations in patients with Emery-Dreifuss muscular dystrophy and functional characterization of four LMNA mutations
.
Hum Mutat
.
2011
;
32
(
2
):
152
67
.
20.
Jimenez-Escrig
A
,
Gobernado
I
,
Garcia‐Villanueva
M
,
Sanchez-Herranz
A
.
Autosomal recessive Emery–Dreifuss muscular dystrophy caused by a novel mutation (R225Q) in the Lamin A/C gene identified by exome sequencing
.
Muscle Nerve
.
avr 2012
;
45
(
4
):
605
10
.
21.
Madej-Pilarczyk
A
.
Clinical aspects of Emery-Dreifuss muscular dystrophy
.
Nucleus
.
2018
;
9
(
1
):
268
74
.
You do not currently have access to this content.