Novel SLC12A1 mutations cause Bartter syndrome in two patients with different prognoses.

Sheng Yi, Mengting Li, Qi Yang, Xiaofei Zhang, Fei Chen, Zailong Qin, Shang Yi, Limei Huang, Hao Wei, Qinle Zhang, Jingsi Luo

Journal: Clinica chimica acta; international journal of clinical chemistry 2022;531():120-125

PMID: 35358470

Full Text on Elsevier Science View on PubMed

Abstract

BACKGROUND

Bartter syndrome is an inherited renal tubular disorder that is characterized by hypokalemic, hypochloremic metabolic alkalosis in which the primary defect is a deficiency of transporters involved in sodium chloride reabsorption. Bartter syndrome type 1 is caused by SLC12A1 mutations.

METHODS

The patients were from two unrelated non-consanguineous Chinese families. Both patients presented with intrauterine growth retardation, premature delivery, failure to thrive, polyuria and metabolic alkalosis. Whole-exome sequencing was used to identify the causative gene.

RESULTS

Exome sequencing identified three novel SLC12A1 mutations in our patients. And we found the two patients had significantly different outcomes when they were two years of age. Moreover, we identified four novel variants of SLC12A1 that were likely to be pathogenic, from our in-house database. A review of the whole-exome sequencing data of patient 1 lead to her brother being genetically diagnosed with pulmonary alveolar microlithiasis, which was caused by compound heterozygous SLC34A2 variations.

CONCLUSION

We reported two children from one family who were affected by different rare conditions. This study expanded the mutation spectra of the SLC12A1 and SLC34A2 genes. We showed the important role of early genetic testing for disease diagnosis and emphasized the importance of standardized treatment and management.

Address: Genetic and Metabolic Central Laboratory, Guangxi Birth Defects Research and Prevention Institute, Maternal and Child Health Hospital of Guangxi Zhuang Autonomous Region, Nanning, China; Guangxi Key Laboratory of Reproductive Health and Birth Defects Prevention, Guangxi Key Laboratory of Precision Medicine for Genetic Diseases, Guangxi Key Laboratory of Birth Defects and Stem Cell Biobank, Guangxi Key Laboratory of Birth Defects Research and Prevention, Maternal and Child Health Hospital of Guangxi Zhuang Autonomous Region, Nanning, China.; Genetic and Metabolic Central Laboratory, Guangxi Birth Defects Research and Prevention Institute, Maternal and Child Health Hospital of Guangxi Zhuang Autonomous Region, Nanning, China; Department of Obstetrics and Gynecology, Key Laboratory for Major Obstetric Diseases of Guangdong Province, The Third Affiliated Hospital of Guangzhou Medical University, Guangzhou, China.; Genetic and Metabolic Central Laboratory, Guangxi Birth Defects Research and Prevention Institute, Maternal and Child Health Hospital of Guangxi Zhuang Autonomous Region, Nanning, China; Pediatrics Department, Maternal and Child Health Hospital of Guangxi Zhuang Autonomous Region, Nanning, China.; Genetic and Metabolic Central Laboratory, Guangxi Birth Defects Research and Prevention Institute, Maternal and Child Health Hospital of Guangxi Zhuang Autonomous Region, Nanning, China; Guangxi Key Laboratory of Reproductive Health and Birth Defects Prevention, Guangxi Key Laboratory of Precision Medicine for Genetic Diseases, Guangxi Key Laboratory of Birth Defects and Stem Cell Biobank, Guangxi Key Laboratory of Birth Defects Research and Prevention, Maternal and Child Health Hospital of Guangxi Zhuang Autonomous Region, Nanning, China. Electronic address: [email protected].

DOI: 10.1016/j.cca.2022.03.025

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MeSH Terms: Alkalosis, Bartter Syndrome, Child, Female, Humans, Male, Mutation, Prognosis, Solute Carrier Family 12, Member 1