Genetic Features of Chinese Patients with Gitelman Syndrome: Sixteen Novel <b><i>SLC12A3</i></b> Mutations Identified in a New Cohort

<b><i>Background:</i></b> Gitelman syndrome (GS) is an autosomal recessive renal tubulopathy caused by inactivating mutations in the <i>SLC12A3</i> gene. Although hundreds of different mutations across the <i>SLC12A3</i> gene have been reported worldwide, data from mainland China are limited. We investigated the clinical manifestations and genetic features of Chinese patients with GS. <b><i>Methods:</i></b> Fifty-four unrelated Chinese patients with clinically diagnosed GS were included. Clinical manifestations and biochemical parameters were collected and analyzed. All exons and flanking regions of the <i>SLC12A3</i> and <i>CLCNKB</i> genes were screened by direct sequencing. <b><i>Results:</i></b> Weakness was the most commonly reported symptom in this cohort of patients with GS. In gender-based analyses, higher systolic blood pressure and urine protein excretion were observed in male patients. For genetic screening, 2 pathogenic <i>SLC12A3</i> mutations were identified in 38 patients (70.4%), 1 mutation in 11 patients (20.4%) and no mutation in 5 patients (9.3%). In total, 42 distinct pathogenic mutations throughout <i>SLC12A3</i> were identified; 16 were novel, including 9 missense, 1 deletion, 1 insertion, 3 splice site and 2 nonsense mutations. Eleven mutations were recurrently found in different patients. Among them, T60M and D486N were identified in 11 individuals. No <i>CLCNKB</i> mutations were found. <b><i>Conclusion:</i></b> Sixteen novel <i>SLC12A3</i> pathogenic mutations were identified in a cohort of Chinese patients with GS. T60M and D486N were most frequent and appear to be important candidate alleles in Chinese patients with GS.