The clinical spectrum and genetic variability of limb-girdle muscular dystrophy in a cohort of Chinese patients

Abstract

BackgroundLimb-girdle muscular dystrophy (LGMD) is a commonly diagnosed hereditary muscular disorder, characterized by the progressive weakness of the limb-girdle muscles. Although the condition has been well-characterized, clinical and genetic heterogeneity can be observed in patients with LGMD. Here, we aimed to describe the clinical manifestations and genetic variability among a cohort of patients with LGMD in South China.ResultsWe analyzed the clinical information, muscle magnetic resonance imaging (MRI) findings, and genetic results obtained from 30 patients (24 families) with clinically suspected LGMD. In 24 probands, 38 variants were found in total, of which 18 were shown to be novel. Among the 30 patients, the most common subtypes were dysferlinopathy in eight (26.67%), sarcoglycanopathies in eight [26.67%; LGMD 2C in three (10.00%), LGMD 2D in three (10.00%), and LGMD 2F in two (6.67%)], LGMD 2A in seven (23.33%), followed by LGMD 1B in three (10.00%), LGMD 2I in three (10.00%), and early onset recessive Emery-Dreifuss-like phenotype without cardiomyopathy in one (3.33%). Furthermore, we also observed novel clinical presentations for LGMD 1B, 2F, and 2I patients with hypermobility of the joints in the upper limbs, a LGMD 2F patient with delayed language development, and other manifestations. Moreover, distinct distributions of fatty infiltration in patients with LGMD 2A, dysferlinopathy, and the early onset recessive Emery-Dreifuss-like phenotype without cardiomyopathy were also observed based on muscle MRI results.ConclusionsIn this study, we expanded the clinical spectrum and genetic variability found in patients with LGMD, which provided additional insights into genotype and phenotype correlations in this disease.Electronic supplementary materialThe online version of this article (10.1186/s13023-018-0859-6) contains supplementary material, which is available to authorized users.

Genetic cause of heterogeneous inherited myopathies in a cohort of Greek patients

“…These advances have led to the realization that defects in a certain gene can cause various myopathic phenotypes, and inversely, the same phenotype can be caused by different pathogenic variants in the same or multiple genes (allelic and locus heterogeneity) [ 3 ]. For instance, LGMDs, characterized by weakness affecting predominantly the shoulder and pelvic girdle muscles, are caused by pathogenic changes in more than 30 genes, with the gene altered and the mode of inheritance determining the LGMD subtype[ [4] , [5] , [6] , [7] , [8] , [9] , [10] , [11] , [12] ].…”

Abnormal Expression of Dysferlin in Blood Monocytes Supports Primary Dysferlinopathy in Patients Confirmed by Genetic Analyses

“…In this study, we identified 13 dysferlin gene mutations, of which nine are novel. Although some studies focused on Chinese patients ( 11 , 12 ), there is no founder mutation reported in this population. The new frameshift and non-sense mutations will cause dysferlinopathy because of the predicted truncation of the protein that will likely result in a complete loss of protein function.…”

“…One approach to identify the underlying mechanisms is to study patient cohorts from different ethnic origins. Different DYSF mutations have been identified in various ethnicities ( 8 – 10 ), although few studies focused on Chinese patients ( 11 , 12 ).…”

Emery–Dreifuss muscular dystrophy: focal point nuclear envelope

“…In addition to 'classical' EDMD, skeletal muscle phenotypes caused by mutations in these genes include, limb-girdle, minimal to no skeletal muscle involvement, and -in the case of LMNA -congenital muscular dystrophy [7,8]. Recently reported cases confirm this phenotypic variability [9,10]; however, the responsible mechanisms remain poorly understood.…”