Chinese Journal of Contemporary Neurology and Neurosurgery ›› 2018, Vol. 18 ›› Issue (8): 595-601. doi: 10.3969/j.issn.1672-6731.2018.08.007

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A novel mutation in GNE gene: clinical characteristics and bioinformatics analysis

WANG Liang1, LI Ya-qin2, ZHANG Hui-li3, ZHU Yu-ling1, HE Ruo-jie1, LI Huan1, LIN Jin-fu1, ZHANG Cheng1   

  1. 1Department of Neurology, the First Affiliated Hospital, Sun Yat - sen University, Guangzhou 510080, Guangdong, China
    2Neuroscience Center, the Seventh Affiliated Hospital, Sun Yat -sen University, Shenzhen 518107, Guangdong, China
    3Department of Neurology, Guangzhou First People's Hospital, Guangzhou Medical University, Guangzhou 510180, Guangdong, China
  • Online:2018-08-25 Published:2018-08-24
  • Contact: ZHANG Cheng (Email: zhangch6@mail.sysu.edu.cn)
  • Supported by:

    This study was supported by the National Natural Science Foundation of China (No. 81471280, 81771359), the National Natural Science Foundation for Young Scientists of China (No. 81601087), and 2015 Production, Study and Research Special Project of Guangzhou, Guangdong Province, China (No. 1561000153).

GNE 基因新发突变致GNE 肌病一例临床表型及生物信息学分析

王倞, 李亚勤, 张惠丽, 朱瑜龄, 何若洁, 李欢, 林金福, 张成   

  1. 510080 广州,中山大学附属第一医院神经科(王倞,朱瑜龄,何若洁,李欢,林金福,张成);518107 深圳,中山大学附属第七医院神经医学中心(李亚勤);510180 广州医科大学附属广州市第一人民医院神经内科(张惠丽)
  • 通讯作者: 张成(Email:zhangch6@mail.sysu.edu.cn)
  • 基金资助:

    国家自然科学基金资助项目(项目编号:81471280);国家自然科学基金资助项目(项目编号: 81771359);国家自然科学基金青年科学基金资助项目(项目编号:81601087);广东省广州市2015 年产学研专项项目(项目编号:1561000153)

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

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