Review and Analysis of Two Gitelman Syndrome Pedigrees Complicated with Proteinuria or Hashimoto’s Thyroiditis Caused by Compound Heterozygous SLC12A3 Mutations
Gitelman syndrome (GS) is an autosomal recessive inherited salt-losing renal tubular disease, which is caused by a pathogenic mutation of SLC12A3 encoding thiazide-sensitive Na-Cl cotransporter, which leads to disturbance of sodium and chlorine reabsorption in renal distal convoluted tubules, result...
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doaj-d84be26035f3487f9d3fd07a81bfdf282021-05-24T00:15:18ZengHindawi LimitedBioMed Research International2314-61412021-01-01202110.1155/2021/9973161Review and Analysis of Two Gitelman Syndrome Pedigrees Complicated with Proteinuria or Hashimoto’s Thyroiditis Caused by Compound Heterozygous SLC12A3 MutationsJian-hui Zhang0Dan-dan Ruan1Ya-nan Hu2Xing-lin Ruan3Yao-bin Zhu4Xiao Yang5Jia-bin Wu6Xin-fu Lin7Jie-wei Luo8Fa-qiang Tang9Shengli Clinical Medical College of Fujian Medical UniversityShengli Clinical Medical College of Fujian Medical UniversityShengli Clinical Medical College of Fujian Medical UniversityDepartment of NeurologyDepartment of Traditional Chinese Medicine the First Affiliated HospitalTeaching and Research Office of Medical CosmetologyShengli Clinical Medical College of Fujian Medical UniversityShengli Clinical Medical College of Fujian Medical UniversityShengli Clinical Medical College of Fujian Medical UniversityShengli Clinical Medical College of Fujian Medical UniversityGitelman syndrome (GS) is an autosomal recessive inherited salt-losing renal tubular disease, which is caused by a pathogenic mutation of SLC12A3 encoding thiazide-sensitive Na-Cl cotransporter, which leads to disturbance of sodium and chlorine reabsorption in renal distal convoluted tubules, resulting in phenotypes such as hypovolemia, renin angiotensin aldosterone system (RAAS) activation, hypokalemia, and metabolic alkalosis. In this study, two GS families with proteinuria or Hashimoto’s thyroiditis were analyzed for genetic-phenotypic association. Sanger sequencing revealed that two probands carried SLC12A3 compound heterozygous mutations, and proband A carried two pathogenic mutations: missense mutation Arg83Gln, splicing mutation, or frameshift mutation NC_000016.10:g.56872655_56872667 (gcggacatttttg>accgaaaatttt) in exon 8. Proband B carries two missense mutations: novel Asp839Val and Arg904Gln. Both probands manifested hypokalemia, hypomagnesemia, hypocalcinuria, metabolic alkalosis, and RAAS activation; in addition, the proband A exhibited decreased urinary chloride, phosphorus, and increased magnesium ions excretion, complicated with Hashimoto’s Thyroiditis, while the proband B exhibited enhanced urine sodium excretion and proteinuria. The older sister of proband B with GS also had Hashimoto’s thyroiditis. Electron microscopy revealed swelling and vacuolar degeneration of glomerular epithelial cells, diffuse proliferation of mesangial cells and matrix, accompanied by a small amount of low-density electron-dense deposition, and segmental fusion of epithelial cell foot processes in proband B. Light microscopy showed mild mesangial hyperplasia in the focal segment of the glomerulus, hyperplasia, and hypertrophy of juxtaglomerular apparatus cells, mild renal tubulointerstitial lesions, and one glomerular sclerosis. So, long-term hypokalemia of GS can cause kidney damage and may also be susceptible to thyroid disease.http://dx.doi.org/10.1155/2021/9973161 |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Jian-hui Zhang Dan-dan Ruan Ya-nan Hu Xing-lin Ruan Yao-bin Zhu Xiao Yang Jia-bin Wu Xin-fu Lin Jie-wei Luo Fa-qiang Tang |
spellingShingle |
Jian-hui Zhang Dan-dan Ruan Ya-nan Hu Xing-lin Ruan Yao-bin Zhu Xiao Yang Jia-bin Wu Xin-fu Lin Jie-wei Luo Fa-qiang Tang Review and Analysis of Two Gitelman Syndrome Pedigrees Complicated with Proteinuria or Hashimoto’s Thyroiditis Caused by Compound Heterozygous SLC12A3 Mutations BioMed Research International |
author_facet |
Jian-hui Zhang Dan-dan Ruan Ya-nan Hu Xing-lin Ruan Yao-bin Zhu Xiao Yang Jia-bin Wu Xin-fu Lin Jie-wei Luo Fa-qiang Tang |
author_sort |
Jian-hui Zhang |
title |
Review and Analysis of Two Gitelman Syndrome Pedigrees Complicated with Proteinuria or Hashimoto’s Thyroiditis Caused by Compound Heterozygous SLC12A3 Mutations |
title_short |
Review and Analysis of Two Gitelman Syndrome Pedigrees Complicated with Proteinuria or Hashimoto’s Thyroiditis Caused by Compound Heterozygous SLC12A3 Mutations |
title_full |
Review and Analysis of Two Gitelman Syndrome Pedigrees Complicated with Proteinuria or Hashimoto’s Thyroiditis Caused by Compound Heterozygous SLC12A3 Mutations |
title_fullStr |
Review and Analysis of Two Gitelman Syndrome Pedigrees Complicated with Proteinuria or Hashimoto’s Thyroiditis Caused by Compound Heterozygous SLC12A3 Mutations |
title_full_unstemmed |
Review and Analysis of Two Gitelman Syndrome Pedigrees Complicated with Proteinuria or Hashimoto’s Thyroiditis Caused by Compound Heterozygous SLC12A3 Mutations |
title_sort |
review and analysis of two gitelman syndrome pedigrees complicated with proteinuria or hashimoto’s thyroiditis caused by compound heterozygous slc12a3 mutations |
publisher |
Hindawi Limited |
series |
BioMed Research International |
issn |
2314-6141 |
publishDate |
2021-01-01 |
description |
Gitelman syndrome (GS) is an autosomal recessive inherited salt-losing renal tubular disease, which is caused by a pathogenic mutation of SLC12A3 encoding thiazide-sensitive Na-Cl cotransporter, which leads to disturbance of sodium and chlorine reabsorption in renal distal convoluted tubules, resulting in phenotypes such as hypovolemia, renin angiotensin aldosterone system (RAAS) activation, hypokalemia, and metabolic alkalosis. In this study, two GS families with proteinuria or Hashimoto’s thyroiditis were analyzed for genetic-phenotypic association. Sanger sequencing revealed that two probands carried SLC12A3 compound heterozygous mutations, and proband A carried two pathogenic mutations: missense mutation Arg83Gln, splicing mutation, or frameshift mutation NC_000016.10:g.56872655_56872667 (gcggacatttttg>accgaaaatttt) in exon 8. Proband B carries two missense mutations: novel Asp839Val and Arg904Gln. Both probands manifested hypokalemia, hypomagnesemia, hypocalcinuria, metabolic alkalosis, and RAAS activation; in addition, the proband A exhibited decreased urinary chloride, phosphorus, and increased magnesium ions excretion, complicated with Hashimoto’s Thyroiditis, while the proband B exhibited enhanced urine sodium excretion and proteinuria. The older sister of proband B with GS also had Hashimoto’s thyroiditis. Electron microscopy revealed swelling and vacuolar degeneration of glomerular epithelial cells, diffuse proliferation of mesangial cells and matrix, accompanied by a small amount of low-density electron-dense deposition, and segmental fusion of epithelial cell foot processes in proband B. Light microscopy showed mild mesangial hyperplasia in the focal segment of the glomerulus, hyperplasia, and hypertrophy of juxtaglomerular apparatus cells, mild renal tubulointerstitial lesions, and one glomerular sclerosis. So, long-term hypokalemia of GS can cause kidney damage and may also be susceptible to thyroid disease. |
url |
http://dx.doi.org/10.1155/2021/9973161 |
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