Founder Mutation for a-sarcoglycan-LGMD2D in a Magdalen Islands Acadian Cluster

Tétreault, Martine; Srour, Myriam; Allyson, J; Thiffault, Isabelle; Loisel, Lina; Robitaille, Yves; Jp, Bouchard; Brais, Bernard

doi:10.1017/s0317167100054135

Cited by 11 publications

(5 citation statements)

References 19 publications

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“…All but one missense mutation affected amino acids positioned in the extracellular domain of α-SG, which is not unexpected because the extracellular domain of α-SG is very large and is constituted by the vast majority of the amino acids of α-SG. The missense mutation c.662G > A in SGCA was the most common mutation found in patients with LGMD2D who originated from East China, whereas the most common mutation is c.101G > T (R34L) in Taiwan [15] and c.229C > T (R77C) in several other countries [2, 46, 51, 52]. Similar to the findings of previous studies [2, 5, 11, 12, 15, 36, 39, 46, 53], the results of our present study suggest that, in contrast with the predominant presence of missense mutations in LGMD2D, null mutations were more prevalent in LGMD2E.…”

Section: Discussionmentioning

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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Section: Discussionmentioning

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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“…[71] Most common mutation in alpha-sarcoglycanopathy is p.R77C[72] with founder effect in Finland[73] and Magdalen. [74] Other founder mutations are p.R34 L in Taiwan[75] and p.R192X in Egypt. [76]…”

Section: Sarcoglycanopathiesmentioning

confidence: 99%

Limb-girdle muscular dystrophies in India: A review

Khadilkar¹,

Faldu²,

Patil³

et al. 2017

Ann Indian Acad Neurol

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Limb-girdle muscular dystrophies (LGMDs) are common in India. Information on LGMDs has been gradually evolving in the recent years. This information is scattered in case series and case studies. The aim of this study is to collate available Indian information on LGMDs and put it in perspective. PubMed search using keywords such as limb-girdle muscular dystrophies in India, sarcoglycanopathies, dysferlinopathy, calpainopathy, and GNE myopathy was carried out. The published information on LGMDs in Indian context suggests that dysferlinopathy, calpainopathy, sarcoglycanopathies, and other myopathies such as GNE myopathy are frequently seen in India. Besides these, anecdotal reports of many other forms are available, some with genetic support and others showing immunocytochemical defects. The genotypic information on LGMDs is gradually evolving and founder mutations have been detected in selected populations. Further multicenter studies are necessary to document the incidence and prevalence of these common conditions in India.

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“…SGCA c.229C>T, p.R77C in exon 3 is a founder mutation from the Magdalen Islands in the Gulf of St. Lawrence. It is the most common SGCA mutation reported internationally . The same mutation was also reported as a founder mutation in several LGMD2D patients from Finland and also from Europe and Brazil .…”

Section: Discussionmentioning

confidence: 68%

Homozygous nonsense mutation inSGCAis a common cause of limb-girdle muscular dystrophy in Assiut, Egypt

et al. 2016

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Introduction The genetic causes of limb-girdle muscular dystrophy (LGMD) have been studied in numerous countries, but such investigations have been limited in Egypt. Methods A cohort of 30 families with suspected LGMD from Assiut, Egypt was studied using immunohistochemistry, homozygosity mapping, Sanger sequencing, and whole exome sequencing. Results Six families were confirmed to have pathogenic mutations, 4 in SGCA and 2 in DMD. Of these, 3 families harbored a single nonsense mutation in SGCA, suggesting that this may be a common mutation in Assiut, Egypt originating from a founder effect. Discussion The Assiut region in Egypt appears to share at least several of the common LGMD genes found in other parts of the world. It is notable that 4 of the 6 mutations were ascertained via whole exome sequencing, even though it was the last approach adopted, illustrating the power of this technique for identifying causative mutations for muscular dystrophies.

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Founder Mutation for a-sarcoglycan-LGMD2D in a Magdalen Islands Acadian Cluster

Cited by 11 publications

References 19 publications

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

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

Limb-girdle muscular dystrophies in India: A review

Homozygous nonsense mutation inSGCAis a common cause of limb-girdle muscular dystrophy in Assiut, Egypt

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