γ‐sarcoglycan and dystrophin mutation spectrum in an Algerian cohort

Dalichaouche, Imene; Sifi, Yamina; Roudaut, Carinne; Sifi, Karima; Hamri, Abdelmadjid; Rouabah, Leila; Abadi, N.; Richard, Isabelle

doi:10.1002/mus.25443

Cited by 11 publications

(7 citation statements)

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“…In a previous publication, a similar mutation landscape was reported. 17 By merging these data, 86% of Algerian patients carry deletions and 14% all others. Figure 2 shows the overview of the mutation landscape in each Eastern European country and in Cyprus.…”

Section: Mutation Frequency and Distribution In Patients With Dmdmentioning

confidence: 99%

Ethnicity-related DMD Genotype Landscapes in European and Non-European Countries

et al. 2021

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ObjectiveGenetic diagnosis and mutation identification are now compulsory for Duchenne (DMD) and Becker muscular dystrophies (BMD), which are due to dystrophin (DMD) gene mutations, either for disease prevention or personalized therapies. To evaluate the ethnic-related genetic assortments of DMD mutations, which may impact on DMD genetic diagnosis pipelines, we studied 328 patients with DMD and BMD from non-European countries.MethodsWe performed a full DMD mutation detection in 328 patients from 10 Eastern European countries (Poland, Hungary, Lithuania, Romania, Serbia, Croatia, Bosnia, Bulgaria, Ukraine, and Russia) and 2 non-European countries (Cyprus and Algeria). We used both conventional methods (multiplex ligation-dependent probe amplification [MLPA] followed by gene-specific sequencing) and whole-exome sequencing (WES) as a pivotal study ran in 28 patients where DMD mutations were already identified by standard techniques. WES output was also interrogated for DMD gene modifiers.ResultsWe identified DMD gene mutations in 222 male patients. We identified a remarkable allele heterogeneity among different populations with a mutation landscape often country specific. We also showed that WES is effective for picking up all DMD deletions and small mutations and its adoption could allow a detection rate close to 90% of all occurring mutations. Gene modifiers haplotypes were identified with some ethnic-specific configurations.ConclusionsOur data provide unreported mutation landscapes in different countries, suggesting that ethnicity may orient genetic diagnosis flowchart, which can be adjusted depending on the mutation type frequency, with impact in drug eligibility.

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Section: Mutation Frequency and Distribution In Patients With Dmdmentioning

confidence: 99%

Ethnicity-related DMD Genotype Landscapes in European and Non-European Countries

et al. 2021

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“…The prevalence of the different sarcoglycans varies across the world. Mutations in α‐SG (LGMDR3) are most prevalent in Europe [4], whereas mutations in γ‐SG (LGMDR5) are most common in the North African population [5]. Mutations in β‐SG (LGMDR4) are represented in different proportions around the world [4,6,7], whereas mutations in δ‐SG (LGMDR6) are almost exclusive to the Brazilian population [8].…”

Section: Introductionmentioning

confidence: 99%

Clinical correlations and long‐term follow‐up in 100 patients with sarcoglycanopathies

Guimarães‐Costa

Fernández‐Eulate

Wahbi

et al. 2020

Euro J of Neurology

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Background and purposeTo describe a large series of patients with α, β, and γ sarcoglycanopathies (LGMD‐R3, R4, and R5) and study phenotypic correlations and disease progression.MethodsA multicentric retrospective study in four centers in the Paris area collecting neuromuscular, respiratory, cardiac, histologic, and genetic data. The primary outcome of progression was age of loss of ambulation (LoA); disease severity was established according to LoA before or after 18 years of age. Time‐to‐event analysis was performed.ResultsOne hundred patients (54 γ‐SG; 41 α‐SG; 5 β‐SG) from 80 families were included. The γ‐SG patients had earlier disease onset than α‐SG patients (5.5 vs. 8 years; p = 0.022) and β‐SG patients (24.4 years). Axial muscle weakness and joint contractures were frequent and exercise intolerance was observed. At mean follow‐up of 22.9 years, 65.3% of patients were wheelchair‐bound (66.7% α‐SG, 67.3% γ‐SG, 40% β‐SG). Dilated cardiomyopathy occurred in all sarcoglycanopathy subtypes, especially in γ‐SG patients (p = 0.01). Thirty patients were ventilated and six died. Absent sarcoglycan protein expression on muscle biopsy and younger age at onset were associated with earlier time to LoA (p = 0.021 and p = 0.002). Age at onset was an independent predictor of both severity and time to LoA (p = 0.0004 and p = 0.009). The α‐SG patients showed genetic heterogeneity, whereas >90% of γ‐SG patients carried the homozygous c.525delT frameshift variant. Five new mutations were identified.ConclusionsThis large multicentric series delineates the clinical spectrum of patients with sarcoglycanopathies. Age at disease onset is an independent predictor of severity of disease and LoA, and should be taken into account in future clinical trials.

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“…The subtypes of sarcoglycanopathy vary in prevalence according to ethnicity and geographic region. LGMD2D is relatively common in Europe and the US [2–4], whereas LGMD2E is most common in the Iranian population [5] and LGMD2C is most common in the Indian [6] and Algeria [7] populations. The typical clinical phenotype of a sarcoglycanopathy includes progressive muscle weakness and atrophy, predominantly of the shoulder and pelvic girdles, and elevated serum creatine kinase (CK).…”

Section: Introductionmentioning

confidence: 99%

Clinical and genetic spectrum of sarcoglycanopathies in a large cohort of Chinese patients

Xie

Hou

et al. 2019

Orphanet J Rare Dis

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Background Sarcoglycanopathies comprise four subtypes of autosomal recessive limb-girdle muscular dystrophy (LGMD2C, LGMD2D, LGMD2E, and LGMD2F) that are caused, respectively, by mutations in the SGCG , SGCA , SGCB , and SGCD genes. Knowledge about the clinical and genetic features of sarcoglycanopathies in Chinese patients is limited. The aims of this study were to investigate in detail the clinical manifestations, sarcoglycan expression, and gene mutations in Chinese patients with sarcoglycanopathies and to identify possible correlations between them. Results Of 3638 patients for suspected neuromuscular diseases (1733 with inherited myopathies, 1557 with acquired myopathies, and 348 unknown), 756 patients had next-generation sequencing (NGS) diagnostic panel. Twenty-five patients with sarcoglycanopathies (11.5%) were identified from 218 confirmed LGMDs, comprising 18 with LGMD2D, 6 with LGMD2E, and one with LGMD2C. One patient with LGMD2D also had Charcot-Marie-Tooth 1A. The clinical phenotypes of the patients with LGMD2D or LGMD2E were markedly heterogeneous. Muscle biopsy showed a dystrophic pattern in 19 patients and mild myopathic changes in 6. The percentage of correct prediction of genotype based on expression of sarcoglycan was 36.0% (4 LGMD2D, 4 LGMD2E, and one LGMD2C). There was a statistically significant positive correlation between reduction of α-sarcoglycan level and disease severity in LGMD2D. Thirty-five mutations were identified in SGCA , SGCB , SGCG , and PMP22 , 16 of which were novel. Exon 3 of SGCA was a hotspot region for mutations in LGMD2D. The missense mutation c.662G > A (p.R221H) was the most common mutation in SGCA . Missense mutations in both alleles of SGCA were associated with a relative benign disease course. No obvious clinical, sarcoglycan expression, and genetic correlation was found in LGMD2E. Conclusions This study expands the clinical and genetic spectrum of sarcoglycanopathies in Chinese patients and provides evidence that disease severity of LGMD2D may be predicted by α-sarcoglycan expression and SGCA mutation. Electronic supplementary material The online version of this article (10.1186/s13023-019-1021-9) contains supplementary material, which is available to authorized users.

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γ‐sarcoglycan and dystrophin mutation spectrum in an Algerian cohort

Cited by 11 publications

References 13 publications

Ethnicity-related DMD Genotype Landscapes in European and Non-European Countries

Ethnicity-related DMD Genotype Landscapes in European and Non-European Countries

Clinical correlations and long‐term follow‐up in 100 patients with sarcoglycanopathies

Clinical and genetic spectrum of sarcoglycanopathies in a large cohort of Chinese patients

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