Abstract：
Sarcoglycanopathies encompass four distinct forms of limb-girdle muscular dystrophies (LGMD), denoted as LGMD R3-R6, arising from mutations within the SGCA, SGCB, SGCG, and SGCD genes. The global prevalence of sarcoglycanopathies is low, making it challenging to study these diseases. The principal objective of this study was to explore the spectrum of mutations in a cohort of Russian patients with sarcoglycanopathies and to ascertain the frequency of these conditions in the Russian Federation. We conducted a retrospective analysis of clinical and molecular genetic data from 49 Russian patients with sarcoglycan genes variants. The results indicated that variants in the SGCA gene were found in 71.4% of cases, with SGCB and SGCG genes each exhibiting variants in 12.2 % of patients. SGCD gene variants were detected in 4.1% of cases. Bi-allelic pathogenic and likely pathogenic variants were identified in 46 of the 49 cases of sarcoglycanopathies: LGMD R3 (n = 34), LGMD R4 (n = 4), LGMD R5 (n = 6), and LGMD R6 (n = 2). A total of 31 distinct variants were identified, comprising 25 previously reported and 6 novel variants. Two major variants, c.229C>T and c.271G>A, were detected within the SGCA, constituting 61.4% of all mutant alleles in Russian patients with LGMD R3. Both LGMD R6 cases were caused by the homozygous nonsense variant c.493C>T p.(Arg165Ter) in the SGCD gene. The incidence of sarcoglycanopathies in the Russian Federation was estimated to be at least 1 in 4,115,039, which is lower than the reported incidence in other populations.
摘要：
肌糖病包括四种不同形式的肢体带肌营养不良（LGMD），表示为LGMDR3-R6，由SGCA内的突变引起，SGCB,SGCG,和SGCD基因。全球的肌糖病患病率很低，使得研究这些疾病具有挑战性。这项研究的主要目的是探索一组俄罗斯肌糖病患者的突变谱，并确定这些疾病在俄罗斯联邦的发生频率。我们对49例俄罗斯sarcogycan基因变异患者的临床和分子遗传学数据进行了回顾性分析。结果表明，在71.4%的病例中发现了SGCA基因的变异，SGCB和SGCG基因在12.2%的患者中都表现出变异。在4.1%的病例中检测到SGCD基因变异。在49例肌糖病中的46例中发现了双等位基因致病性和可能的致病性变异：LGMDR3（n=34），LGMDR4（n=4），LGMDR5（n=6），和LGMDR6(n=2)。总共鉴定了31种不同的变体，包含25个先前报道的和6个新的变体。两个主要的变体,c.229C>T和c.271G>A，在SGCA中检测到，占俄罗斯LGMDR3患者所有突变等位基因的61.4%。两个LGMDR6病例均由SGCD基因中的纯合无义变体c.493C>Tp。（Arg165Ter）引起。据估计，俄罗斯联邦的肌糖病发病率至少为4,115,039人中有1人，低于其他人群的报告发病率。
