背景:由于临床表型和肌肉组织病理学表现重叠,遗传性肌病的诊断通常具有挑战性。这项回顾性研究旨在确定利雅得三级医院遗传性肌病的表型和基因型谱,沙特阿拉伯。
方法:我们回顾了2018年1月至2022年12月期间评估的遗传性肌病患者的医疗记录。
结果:包括87例患者(78个家庭),三分之二为男性,平均年龄为35岁(SD14.2)。四肢肌营养不良(LGMD)是最普遍的临床诊断(25例;29%),谁,22例患者中有15例(68%)获得了基因诊断.在基因证实的LGMD中,最普遍的疾病是铁代谢异常(27%),其次是Fukutin相关蛋白(FKRP)相关的肢带肌营养不良(20%),肌糖病(20%),层粘连蛋白A/C相关肌病(13%),和calpain-3肌病(13%)。在26例具有致病性/可能的致病性变异的患者中,基因检测方法是全外显子组测序(WES)(42%),下一代测序(NGS)(31%),和靶向单基因分析(27%)。每种基因检测方法的灵敏度如下:100%用于靶向单基因分析,100%用于D4Z4重复阵列单元的靶向分析,88%用于强直性肌营养不良蛋白激酶(DMPK)重复扩增分析,NGS-神经肌肉小组为42%,和46%的WES。
结论:遗传性肌病的流行类型与当地和国际报道的一致。这项研究强调了在成人队列中诊断遗传性肌病的各种分子遗传测试的诊断率,以及在怀疑患有面肩肱肌营养不良(FSHD)或线粒体肌病的情况下,需要改善对高级分子测试的访问。
BACKGROUND: Diagnosis of hereditary myopathy is often challenging owing to overlapping clinical phenotypes and muscle histopathological findings. This retrospective study aimed to identify the phenotypic and genotypic spectra of hereditary myopathies at a tertiary hospital in Riyadh, Saudi Arabia.
METHODS: We reviewed the medical records of patients with hereditary myopathy who were evaluated between January 2018 and December 2022.
RESULTS: Eighty-seven patients (78 families) were included, two-thirds were men with a mean age of 35 (SD 14.2) years. Limb-girdle muscular dystrophy (LGMD) was the most prevalent clinical diagnosis (25 cases; 29%), of whom, a genetic diagnosis was achieved in 15 of 22 patients tested (68%). In genetically confirmed LGMD, the most prevalent disorders were dysferlinopathy (27%) followed by fukutin-related protein (FKRP) - related limb girdle muscular dystrophy (20%), sarcoglycanopathy (20%), lamin A/C related myopathy (13%), and calpain-3 myopathy (13%). In 26 patients with pathogenic/likely pathogenic variants, the genetic testing method was whole exome sequencing (WES) (42%), Next generation sequencing (NGS) (31%), and targeted single gene analysis (27%). The sensitivity of each genetic testing method was as follows: 100% for targeted single-gene analysis, 100% for targeted analysis of D4Z4 repeat array units, 88% for myotonic dystrophy protein kinase (DMPK) repeat expansion analysis, 42% for NGS-neuromuscular panel, and 46% for WES.
CONCLUSIONS: The prevalent types of hereditary myopathies were consistent with those reported locally and internationally. This study highlights the diagnostic yield of various molecular genetic tests for the diagnosis of hereditary myopathy in an adult cohort and the need for improved access to advanced molecular testing in cases suspected to have facioscapulohumeral muscular dystrophy (FSHD) or mitochondrial myopathies.