上海交通大学学报（医学版）

›› 2009, Vol. 29 ›› Issue (11): 1344-.

• 论著（临床研究） • 上一篇    下一篇

低钾失盐性肾小管病患者WNK基因突变研究

张 翀, 秦 岭, 邵乐平, 王朝晖, 王伟铭, 任 红, 张 文, 严富洪, 谢静远, 陈 楠   

  1. 上海交通大学 医学院瑞金医院 肾脏内科, 上海 200025
  • 出版日期:2009-11-25 发布日期:2009-11-24
  • 通讯作者: 陈 楠, 电子信箱: chen-nan@medmail.com.cn。
  • 作者简介:张 翀（1972—）, 男, 博士, 副主任医师；电子信箱: zhangchong2005@yahoo.com.cn。
  • 基金资助:

    上海市科委重点项目（07JC14037）和上海市科委重大项目（08dz1900502）

Mutations of WNK gene in patients with hypokalemic salt-losing tubulopathies

ZHANG Chong, QIN Ling, SHAO Le-ping, WANG Zhao-hui, WANG Wei-ming, REN Hong, ZHANG Wen, YAN Fu-hong, XIE Jing-yuan, CHEN Nan   

  1. Department of Nephrology, Ruijin Hospital, School of Medicine, Shanghai Jiaotong University, Shanghai 200025, China
  • Online:2009-11-25 Published:2009-11-24
  • Supported by:

    Shanghai Science and Technology Committee Foundation, 07JC14037, 08dz1900502

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摘要：

目的 通过对低钾失盐性肾小管病(SLTs)家系WNK基因外显子扩增测序，初步探讨SLTs的分子遗传学机制。方法 以经CLCNKB和SLC12A3基因测序不符合典型Bartter综合征或Gitelman综合征基因型的8个SLTs家系为研究对象，抽提患者及患病/非患病亲属的外周血DNA，设计引物扩增WNK4和WNK1的外显子序列，送测序并进行序列比对。结果 对8个SLTs家系的WNK基因扫描发现2个WNK1杂合错义突变，分别为Ile1172→Met (I1172M)和Ser2047→Asn (S2047N)，且仅存在于家系患病者中，非患病家族成员及正常对照中均未检出。结论 在8个SLTs 家系患病者中发现2个伴氨基酸改变的WNK1杂合突变（I1172M和S2047N），提示WNK激酶可能是非婴儿期SLTs的第三个致病基因。

关键词: 低钾失盐性肾小管病, WNK激酶, 突变, 测序

Abstract:

Objective To explore the molecular mechanisms involved in hypokalemic salt-losing tubulopathies (SLTs) through genetic screening of WNK gene in patients with SLTs. Methods Forty-four kindreds of SLTs were diagnosed Batter's syndrome or Gitelman's syndrome after CLCNKB and SLC12A3 sequencing and analysis, 8 of whose phenotype can not be simply attributed to CLCNKB or SLC12A3 mutations. Primers for PCRamplified exons of WNK4 and WNK1 gene in genomic DNA were designed, and direct sequencing was performed to analyse the PCR products. Results Two missense mutations of WNK1, Ile1172→Met (I1172M) and Ser2047→Asn (S2047N), were identified. Both of these 2 mutations segregated with the disease in SLTs kindred. Conclusion Two heterozygote missense mutations of WNK1 gene (I1172M and S2047N) were found in 8 SLTs kindreds, indicating that WNK1 might be another gene responsible for hypokalemic salt-losing tubulopathies.

Key words: hypokalemic salt-losing tubulopathies, WNK kinase, mutation, sequencing