摘要：

目的 报告1例GNE 肌病患者，总结其临床表型和基因型特征，扩展GNE 基因突变谱。方法与结果 男性患者，33 岁，双下肢远端对称性无力，以小腿前群肌显著，缓慢进展；父母为近亲婚配；血清肌酸激酶升高（1139U/L）；肌电图呈肌源性损害；双下肢CT 显示轻度肌萎缩；肌肉组织活检可见肌纤维大小不等，肌细胞核内移，约2%的肌纤维存在镶边空泡；基因检测显示，患者存在GNE 基因外显子9 c.1624C > T（p.Pro542Ser）纯合突变，其母、其子和其女均携带GNE 基因外显子9 c.1624C > T（p. Pro542Ser）杂合突变，该突变尚未报道，经生物信息学分析判断为有害，根据美国医学遗传学和基因组学会指南判断为Ⅱ类可能的致病性突变。患者最终明确诊断为GNE 肌病，该家系明确诊断为GNE 肌病家系。结论 本研究系统报道1例GNE 肌病患者的基因型和临床表型信息，扩展GNE 基因突变谱，加深临床医师对疾病的认识。

关键词: 肌疾病, 表型, 基因, 突变, 计算生物学

Abstract:

Objective To report and summarize clinical phenotype and genotype characteristics in a patient with GNE myopathy, and to extend mutation spectrum of GNE gene. Methods and Results A male patient, 33 years, characterized by symmetric weakness of bilateral distal lower limbs, especially in anterior group of calf muscles, which was progressive slowly. His parents were consanguineous. The level of serum creatine kinase (CK) was elevated (1139 U/L); electromyography (EMG) presented with myogenic injury; CT results of bilateral lower limbs showed mild muscle atrophy; muscle histology showed dramatically varied sizes of myofibers, centralization of myonuclei, rimmed vacuoles in about 2% of myofibers; genetic testing exhibited homozygous mutation [GNE gene, exon 9, c.1624C > T (p.Pro542Ser)] in the proband and heterozygous mutation [GNE gene, exon 9, c.1624C > T (p.Pro542Ser)] in the proband's mother, son and daughter. This mutation had not been reported and was malignant according to bioinformatics analysis. Furthermore, the mutation was likely pathogenic ( Ⅱ) on the basis of American College of Medical Genetics and Genomics (ACMG) guideline. Thus, the patient was diagnosed as GNE myopathy, and the family was a pedigree with GNE myopathy. Conclusions This study systematically reports genotype and phenotype information of a patient with GNE myopathy, which extends mutation spectrum of GNE gene and improves the understandings of clinic practitioner for GNE myopathy.

Key words: Muscular diseases, Phenotype, Genes, Mutation, Computational biology