Xin Wang1, Yu Ding2, Qi Liu3, Guocan Yang4. 1. Department of Rheumatology, Shaoxing People's Hospital (Shaoxing Hospital, Zhejiang University School of Medicine), 312000, Shaoxing, People's Republic of China. 2. Central Laboratory, Hangzhou First People's Hospital, Zhejiang University School of Medicine, 310006, Hangzhou, People's Republic of China. 3. Department of Transfusion, Shaoxing People's Hospital (Shaoxing Hospital, Zhejiang University School of Medicine), 312000, Shaoxing, People's Republic of China. jokaing@163.com. 4. Department of Transfusion, Shaoxing People's Hospital (Shaoxing Hospital, Zhejiang University School of Medicine), 312000, Shaoxing, People's Republic of China. sxyangguocan@protonmail.com.
Abstract
PURPOSE: Gitelman syndrome (GS) is an autosomal recessive renal tubular disorder characterized by salt wasting and hypokalemia resulting from loss-of-function mutations in the solute carrier family 12A3 (SLC12A3) gene encoding the thiazide-sensitive NaCl cotransporter (NCC). Here, we investigated the clinical manifestations and genetic features of a Chinese pedigree with GS. METHODS: Next-generation sequencing and Sanger sequencing analysis were performed to define and confirm the SLC12A3 gene mutations of the patient (proband II:1) and this pedigree. Clinical manifestations and biochemical parameters were collected and analyzed. RESULTS: Genetic analysis of the SLC12A3 gene identified two novel mutations in the proband, heterozygous (c.2842delT) and heterozygous (c.1569_1586del) mutation, respectively. Additionally, heterozygous (c.2842delT) mutation in SLC12A3 gene was found in his father and younger brother. The other heterozygous (c.1569_1586del) mutation in SLC12A3 gene was carried by his mother. CONCLUSIONS: Two novel mutations may be related to the occurrence of the GS in the pedigree. However, additional studies are particularly required to explore the underlying molecular mechanisms.
PURPOSE: Gitelman syndrome (GS) is an autosomal recessive renal tubular disorder characterized by salt wasting and hypokalemia resulting from loss-of-function mutations in the solute carrier family 12A3 (SLC12A3) gene encoding the thiazide-sensitive NaCl cotransporter (NCC). Here, we investigated the clinical manifestations and genetic features of a Chinese pedigree with GS. METHODS: Next-generation sequencing and Sanger sequencing analysis were performed to define and confirm the SLC12A3 gene mutations of the patient (proband II:1) and this pedigree. Clinical manifestations and biochemical parameters were collected and analyzed. RESULTS: Genetic analysis of the SLC12A3 gene identified two novel mutations in the proband, heterozygous (c.2842delT) and heterozygous (c.1569_1586del) mutation, respectively. Additionally, heterozygous (c.2842delT) mutation in SLC12A3 gene was found in his father and younger brother. The other heterozygous (c.1569_1586del) mutation in SLC12A3 gene was carried by his mother. CONCLUSIONS: Two novel mutations may be related to the occurrence of the GS in the pedigree. However, additional studies are particularly required to explore the underlying molecular mechanisms.
Authors: Daniel Stewart; Daniela Iancu; Emma Ashton; Aisling E Courtney; Andrew Connor; Stephen B Walsh Journal: Am J Kidney Dis Date: 2018-09-07 Impact factor: 8.860
Authors: Patrick R Walsh; Yincent Tse; Emma Ashton; Daniela Iancu; Lucy Jenkins; Marc Bienias; Robert Kleta; William Van't Hoff; Detlef Bockenhauer Journal: Clin Kidney J Date: 2017-11-10