印度患者的肌糖病的临床遗传学结构仅报道为短系列。在本研究中,我们的目的是调查临床表现,遗传基础,和患者的疾病进展遗传证实有肌糖病变。在68名疑似肌糖病变的先证者中进行了下一代测序。在68个先证者的肌聚糖基因中检测到总共35种不同的变体(M=37;年龄范围,5-50年)。44个家庭都有血缘关系。预测32种变体是致病性/可能致病性的,其中报告了25个(78.13%),和7(21.87%)是新颖的。在总共64位(94.12%)具有双等位基因变异的先证者中确认了临床诊断[SGCA(n=18);SGCB(n=34);SGCG(n=7);SGCD(n=5)]。最常见的突变是c.54A>C(p。SGCB中的Thr182Pro),在20例患者中检测到(29.42%)。大多数致病突变是纯合的(n=30;93.75%)。4种情况下的变体具有不确定的意义。33例患者在平均年龄15.12±9.47岁时失去了下床活动,发病7.76±5.95年后。只有2名患者有心脏症状,其中一人有呼吸肌受累。这项研究的结果表明,SGCB中的突变是最常见的,其次是SGCA,SGCG,SGCD。这项研究中发现的新变异扩展了肌糖病的突变谱。据我们所知,这是印度的第一项研究,该研究描述了大量经遗传证实的肌糖病患者,并报告了其疾病进展.
The clinico-genetic architecture of sarcoglycanopathies in Indian patients is reported only as short series. In the present study, we aimed to investigate the clinical picture, genetic basis, and disease progression of patients genetically confirmed to have
sarcoglycanopathy. Next-generation sequencing was performed in 68 probands with suspected
sarcoglycanopathy. A total of 35 different variants were detected in the sarcoglycan genes in 68 probands (M = 37; age range, 5-50 years). Consanguinity was present in 44 families. Thirty-two variants are predicted to be pathogenic/likely pathogenic, among which 25 (78.13%) are reported, and 7 (21.87%) are novel. The clinical diagnosis was confirmed in a total of 64 (94.12%) probands with biallelic variations [SGCA(n=18); SGCB(n=34); SGCG(n=7); SGCD(n=5)]. The most common mutation was c.544A > C (p.Thr182Pro) in SGCB, and detected in 20 patients (29.42%). The majority of pathogenic mutations are homozygous (n = 30; 93.75%). Variants in 4 cases are of uncertain significance. Thirty-three patients lost ambulation at a mean age of 15.12 ± 9.47 years, after 7.76 ± 5.95 years into the illness. Only 2 patients had cardiac symptoms, and one had respiratory muscle involvement. The results from this study suggest that mutations in SGCB are most common, followed by SGCA, SGCG, and SGCD. The novel variations identified in this study expand the mutational spectrum of sarcoglycanopathies. To the best of our knowledge, this is the first study from India to describe a large cohort of genetically confirmed patients with
sarcoglycanopathy and report its disease progression.