Abstract
BackgroundLimb-girdle muscular dystrophy (LGMD) is a genetically heterogeneous, hereditary disease characterized by limb-girdle weakness and histologically dystrophic changes. The prevalence of each subtype of LGMD varies among different ethnic populations. This study for the first time analyzed the phenotypes and genotypes in Taiwanese patients with LGMD in a referral center for neuromuscular diseases (NMDs).ResultsWe enrolled 102 patients clinically suspected of having LGMD who underwent muscle biopsy with subsequent genetic analysis in the previous 10 years. On the basis of different pathological categories, we performed sequencing of target genes or panel for NMDs and then identified patients with type 1B, 1E, 2A, 2B, 2D, 2I, 2G, 2 N, and 2Q. The 1B patients with LMNA mutation presented with mild limb-girdle weakness but no conduction defect at the time. All 1E patients with DES mutation exhibited predominantly proximal weakness along with distal weakness. In our cohort, 2B and 2I were the most frequent forms of LGMD; several common or founder mutations were identified, including c.1097_1099delACA (p.Asn366del) in DES, homozygous c.101G > T (p.Arg34Leu) in SGCA, homozygous c.26_33dup (p.Glu12Argfs*20) in TCAP, c.545A > G (p.Tyr182Cys), and c.948delC (p.Cys317Alafs*111) in FKRP. Clinically, the prevalence of dilated cardiomyopathy in our patients with LGMD2I aged > 18 years was 100%, much higher than that in European cohorts. The only patient with LGMD2Q with PLEC mutation did not exhibit skin lesions or gastrointestinal abnormalities but had mild facial weakness. Muscle imaging of LGMD1E and 2G revealed a more uniform involvement than did other LGMD types.ConclusionOur study revealed that detailed clinical manifestation together with muscle pathology and imaging remain critical in guiding further molecular analyses and are crucial for establishing genotype–phenotype correlations. We also determined the common mutations and prevalence for different subtypes of LGMD in our cohort, which could be useful when providing specific care and personalized therapy to patients with LGMD.
Highlights
Limb-girdle muscular dystrophy (LGMD) is a genetically heterogeneous, hereditary disease characterized by limb-girdle weakness and histologically dystrophic changes
On the basis of muscle pathology, patients were first categorized into seven groups according to dystrophic changes with (1) dystrophin deficiency, (2) dysferlin deficiency, (3) sarcoglycan deficiency, (4) alpha-dystroglycan deficiency, (5) markedly disorganized myofibrillar network with or without cytoplasmic body and rimmed vacuole, (6) numerous lobulated fibers, and (7) others (Fig. 1)
For group 1 (n = 21), following genetic analysis of DMD have confirmed the diagnosis of dystrophinopathy for these patients, including 13 Duchenne-type and 8 Becker-type muscular dystrophy
Summary
Limb-girdle muscular dystrophy (LGMD) is a genetically heterogeneous, hereditary disease characterized by limb-girdle weakness and histologically dystrophic changes. The prevalence of each subtype of LGMD varies among different ethnic populations. Limb-girdle muscular dystrophy (LGMD) refers to a group of genetically heterogeneous, hereditary muscle diseases characterized by clinically progressive girdle weakness and pathologically dystrophic change. The LGMD spectrum has rapidly expanded in the past 10 years because of methodological advancements in genetic testing, such as next-generation sequencing (NGS). LGMD prevalence varies greatly among different geographic areas and subtypes. This might partly result from the existence of founder mutation and consanguineous marriage in certain geographic regions and ethnic populations [3]. A meta-analysis on the epidemiology of muscular dystrophy estimated the prevalence of LGMD at approximately 1.63 per 100,000 [4]. Integrated data regarding LGMD epidemiology is sparse in Asian countries [13, 14]
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