Department of Pediatrics, Peking University First Hospital, Beijing, China.
Department of Neurology, Peking Union Medical College Hospital, Peking Union Medical College and Chinese Academy of Medical Sciences, Beijing, China.
Clin Genet. 2021 Mar;99(3):384-395. doi: 10.1111/cge.13886. Epub 2021 Jan 19.
Dystroglycanopathy is a group of muscular dystrophies with deficient glycosylation of alpha-dystroglycan (α-DG). We recruited patients from 36 tertiary academic hospitals in China. In total, 143 patients with genetically diagnosed dystroglycanopathy were enrolled. Of these, limb girdle muscular dystrophy was the most common initial diagnosis (83 patients) and Walker-Warburg syndrome was the least common (1 patient). In 143 patients, mutations in FKRP gene were the most prevalent (62 patients), followed by POMT2, POMT1 (16), POMGNT1, ISPD (14), FKTN, GMPPB, B3GALNT2, DPM3, and DAG1. Several frequent mutations were identified in FKRP, POMT1, POMGNT1, ISPD, and FKTN genes. Many of these were founder mutations. Patients with FKRP mutations tended to have milder phenotypes, while those with mutations in POMGNT1 genes had more severe phenotypes. Mental retardation was a clinical feature associated with mutations of POMT1 gene. Detailed clinical data of 83 patients followed up in Peking University First Hospital were further analyzed. Our clinical and genetic analysis of a large cohort of Chinese patients with dystroglycanopathy expanded the genotype variation and clinical spectrum of congenital muscular dystrophies.
肌营养不良症是一组由于α- 肌聚糖（α-DG）糖基化缺陷导致的肌肉疾病。我们从中国 36 家三甲医院招募了患者。总共纳入了 143 例经基因诊断的肌营养不良症患者。其中，肢带型肌营养不良症是最常见的初始诊断（83 例），而沃克- 沃伯格综合征是最少见的（1 例）。在 143 例患者中，FKRP 基因突变最常见（62 例），其次是 POMT2、POMT1（16 例）、POMGNT1、ISPD（14 例）、FKTN、GMPPB、B3GALNT2、DPM3 和 DAG1。FKRP、POMT1、POMGNT1、ISPD 和 FKTN 基因中存在一些常见的突变。其中许多是创始性突变。FKRP 基因突变的患者表型往往较轻，而 POMGNT1 基因突变的患者表型则更为严重。智力迟钝是与 POMT1 基因突变相关的临床特征。对在北京大学第一医院接受随访的 83 例患者的详细临床数据进行了进一步分析。我们对一大组中国肌营养不良症患者的临床和遗传分析扩大了先天性肌肉疾病的基因型变异和临床谱。
