Abstract:

Objective: To summarize the experience of molecular genetic analysis of two patients with Gitelman syndrome. Methods: Two patients admitted to our hospital due to recurrent hypokalemia were highly suspected as Gitelman syndrome in clinical. Peripheral venous blood samples were collected from the patients and their parents. Genomic DNA was extracted and analyzed by whole exome sequencing(WES). Results: The trio-WES analysis showed that two patients had the compound heterozygous variations in the SLC12A3 gene. The variation sites were c.965 -1_976delinsACCGAAAATTTT and c.1964G >A in one patient, and c.486_491delinsAC and c.2178+1G>T in another patient. Both parents were carriers of the mutant sites with normal phenotypes. The results of Sanger sequencing were consistent with those of trio-WES. Conclusions: The compound heterozygous pathogenic variations in the SLC12A3 gene may be the genetic cause of these two patients, which expands the spectrum of pathogenic variations of this gene. For those patient suspected as Gitelman syndrome, the genetic testing of the patient and parents should be completed, so as to make a clear diagnosis, provide more comprehensive genetic counseling and more accurate prenatal diagnosis for subsequent pregnancies.

Key words: Gitelman syndrome, Solute carrier family 12, member 3, Whole exome sequencing, Mutation, Hypokalemia