临床儿科杂志 ›› 2020, Vol. 38 ›› Issue (2): 120-.doi: 10.3969/j.issn.1000-3606.2020.02.011

• 综合报道 • 上一篇    下一篇

丙酮酸激酶缺乏症2 家系基因变异分析

邱局,程首超   

  1. 咸宁市中心医院 湖北科技学院附属第一医院 (湖北咸宁 437100)
  • 发布日期:2020-02-20
  • 通讯作者: 程首超 电子信箱:qiujux1@126.com

Clinical and genetic analysis of two patients with pyruvate kinase deficiency caused by PKLR gene  mutation

Qiu Ju, Cheng Shouchao   

  1. Xianning Central Hospital, The First Hospital of Hubei University of Science and Technology, Xianning 437100, Hubei, China
  • Published:2020-02-20

摘要:  目的 探讨丙酮酸激酶缺乏症(PKD)的临床及遗传学特点。方法 回顾分析2例PKD患儿的临床资料,复 习相关文献总结PKD的临床及遗传学特点。结果 2例患儿均为女孩,年龄3岁8个月和3岁10个月;均表现为巩膜黄染, 中度贫血(血红蛋白<60 g/L)。 全外显子测序分析发现,例1的PKLR基因存在c.106G>T以及c.817C>T复合杂合突变, 其中c.106G>T突变遗传自父亲,而c.817C>T遗传自母亲,患儿姑姑为c.106G>T突变携带者;例2 PKLR基因存在c.1279G>T 以及IVS6-1G>T复合杂合突变,其中c.1279G>T突变遗传自母亲,IVS6-1G>T突变遗传自父亲。例1的复合杂合突变未 影响患者PKLR基因表达,而例2剪接位点IVS6-1G>T突变可能影响PKLR基因的RNA水平。结论 两个PKD家系均为 PKLR基因变异,基因检测有助PKD诊断。

关键词:  丙酮酸激酶缺乏症; PKLR基因; 临床特点; 突变

Abstract:  Objective To investigate the clinical features of two patients diagnosed with pyruvate kinase deficiency caused by PKLR gene mutation. Method Clinical data of the patients was retrospectively analyzed. Genetic test was performed using the whole exome sequencing (WES), and Sanger sequencing was used to verify the results. Related literatures on clinical and genetic features of pyruvate kinase deficiency were reviewed. Results Two female patients with three years and eight months old respectively, suffered from a sallow complexion for three years were recruited in this study. The clinical manifestations of the children were moderate anemia, yellow sclera and low hemoglobin levels (all below 60g/L) as indicated by routine blood tests. Compound heterozygous mutations of c.106G>T inherited from her mother and c.817C>T inherited from her father in PKLR gene were found by the whole exome sequence, and two heterozygous mutations of c.1279G>T inherited from her mother and IVS6-1G>T inherited from her father IVS6-1G>Tin PKLR gene were found in patient 2. In silico analysis showed that mutation may affect protein function, and IVS6-1G>T mutation may affect splicing. Conclusion The mutations of PKLR gene is the pathogenesis of two PKD families. Genetic test could help diagnosis in patients with PKD.

Key words:  pyruvate kinase deficiency; PKLR gene; clinical phenotype; mutation