第七届北京罕见病学术大会暨2019京津冀罕见病学术大会征文（126）

1Department of Neurology， Peking University First Hospital， Beijing

2Department of Pediatrics， Peking University First Hospital， Beijing

Xie ZY1， Yu M1， Wang ZX1， Zhang W1， Xiong H2， Yuan Y1

The aim of this study was to determine the clinical and genetic spectrum of sarcoglycanopathies in Chinese patients. Screening of 3638 patients for suspected neuromuscular disease identified 25 with sarcoglycanopathies， comprising 18 with limb-girdle muscular dystrophy 2D (LGMD2D)， 6 with LGMD2E， and one with LGMD2C. One patient with LGMD2D also had Charcot-Marie-Tooth 1A. All patients underwent extensive clinical evaluation and review of their medical records. Disease severity was defined by hierarchical analysis. Genetic analysis and muscle biopsies were performed in all cases. The clinical phenotypes of the patients with LGMD2D or ?LGMD2E were markedly heterogeneous. Muscle biopsy showed a dystrophic pattern in 19 patients and mild myopathic changes in 6. The percentage of correct prediction of genotype based on expression of sarcoglycan was 36.0% (4 LGMD2D， 4 LGMD2E， and one LGMD2C). There was a statistically significant positive correlation between reduction of α-sarcoglycan level and disease severity in LGMD2D. Thirty-five mutations were identified in SGCA， SGCB， SGCG， and PMP22， 16 of which were novel. Exon 3 of SGCA was a hotspot region for mutations in LGMD2D.The missense mutation c.662G>A (p.R221H) was the most common mutation in SGCA. Missense mutations in both alleles of SGCA were associated with a relative benign disease course. No obvious clinical， sarcoglycan expression， and genetic correlation was found in LGMD2E. This study expands the clinical and genetic spectrum of sarcoglycanopathies in Chinese patients and provides evidence that disease severity of LGMD2D may be predicted by α-sarcoglycan expression and SGCA mutation.