Mathur Priyanshu, Kaur Ashmeet, Vijay Urvashi, Gupta Ashok, Agarwal Kamlesh, Agrawal Lokesh
Department of Pediatrics, SMS Medical College and Hospital, Jaipur 302020, Rajasthan, India.
Department of Pathology, SMS Medical College and Hospital, Jaipur 302020, Rajasthan, India.
Glob Med Genet. 2024 Dec 16;12(1):100035. doi: 10.1016/j.gmg.2024.100035. eCollection 2025 Mar.
Limb-Girdle Muscular Dystrophy (LGMD) is a rare heterogeneous group of neuromuscular disorders distinguished by progressive weakness of limb-girdle muscles. Diagnosis of LGMD is a challenging task and requires multiple obligatory assays.
To study the epidemiology, clinical features, the genetic variability in patients diagnosed with LGMD through Next Generation Sequencing.Material and MethodA retrospective study of 27 patients suspected of LGMD was done to study the phenotypic presentation and the genotypic alteration of the patients, presenting to a tertiary care center in Rajasthan were studied.
Out of the twenty-seven patients suspected of LGMD, nineteen patients took genetic tests, while eight patients underwent biopsy. Among the nineteen patients, seventeen patients were identified with pathogenic mutations. Autosomal Recessive (LGMD-R) was the most common subgroup in this cohort. In the LGMD R1 subgroup, the most common mutation was c.2051-1 G>T and the exon hotspot was 18-22. The deleterious mutations in the LGMD R2 subgroup were distributed along the entire coding sequence, without any hotspot. However, C2E, C2F, and DysF domains contain variants at higher frequencies. The types of mutations were mostly point mutations (34 % of missense mutations and 66 % of nonsense mutations). We identified one novel mutation which was considered as a stop codon. Patients(n = 8) who underwent muscle biopsy for immunohistochemistry, had absent/reduced sarcoglycan uptake (n = 4) or absent dysferlin (n = 2) on the sarcolemma, while the remaining two biopsies were inconclusive (due to multiple protein deficiencies).
肢带型肌营养不良（LGMD）是一组罕见的异质性神经肌肉疾病，其特征为肢带肌肉进行性无力。LGMD的诊断是一项具有挑战性的任务，需要多种必要的检测。
通过下一代测序研究诊断为LGMD的患者的流行病学、临床特征和基因变异性。材料与方法对27例疑似LGMD的患者进行回顾性研究，以研究在拉贾斯坦邦一家三级医疗中心就诊的患者的表型表现和基因型改变。
在27例疑似LGMD的患者中，19例进行了基因检测，8例接受了活检。在这19例患者中，17例被鉴定出致病突变。常染色体隐性遗传（LGMD-R）是该队列中最常见的亚组。在LGMD R1亚组中，最常见的突变是c.2051-1 G>T，外显子热点为18-22。LGMD R2亚组中的有害突变分布在整个编码序列中，没有任何热点。然而，C2E、C2F和DysF结构域含有较高频率的变异。突变类型大多为点突变（错义突变占34%，无义突变占66%）。我们鉴定出一个新的突变，被认为是一个终止密码子。接受肌肉活检进行免疫组织化学检测的患者（n = 8），肌膜上有肌聚糖摄取缺失/减少（n = 4）或dysferlin缺失（n = 2），而其余两次活检结果不明确（由于多种蛋白质缺乏）。
