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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。
Objective To explore the molecular genetic mechanism of SLTs by exon sequencing of WNK gene in families with low potassium salt-losing tubulopathy (SLTs). Methods Totally 8 SLTs pedigrees which did not accord with the typical Bartter syndrome or Gitelman syndrome genotypes were sequenced by CLCNKB and SLC12A3. DNA from peripheral blood of patients and relatives of diseased / non-diseased patients was extracted. Primers were designed to amplify WNK4 And WNK1 exon sequences, sent sequencing and sequence alignment. Results Two WNK1 heterozygous missense mutations were found in the WNK gene of eight SLTs pedigrees, which were Ile1172 → Met (I1172M) and Ser2047 → Asn (S2047N), respectively, which were only found in pedigrees with non-affected families Members and normal controls were not detected. Conclusions Two WNK1 heterozygous mutations with amino acid changes (I1172M and S2047N) were found in eight SLTs pedigrees, suggesting that WNK kinase may be the third causative gene of non-infant SLTs.