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