title: A novel SLC12A1 gene mutation associated with hyperparathyroidism, hypercalcemia, nephrogenic diabetes insipidus, and nephrocalcinosis in four patients.
abstract: Solute Carrier Family 12 member 1 (SLC12A1) gene encodes the sodium-potassium-chloride co-transporter (NKCC2) at the apical membrane of the thick ascending loop of Henle (TAL). Bartter's syndrome (BS) type I is a rare, autosomal recessive, renal tubular disorder associated with mutation of the SLC12A1 gene. Presenting features include: hypokalemic metabolic alkalosis, hypercalciuria and nephrocalcinosis. The many allelic variants reported present with a spectrum of phenotypes, biochemical abnormalities and clinical severities. However, to date, only two reports have described hyperparathyroidism and hypercalcemia in patients with SLC12A1 gene mutations. We describe 4 patients with 4 novel mutation variants in the SLC12A1 gene (c.735C>G, c.1137del, c.2498-2499del, and c.1833delT) presenting with variable degrees of hyperparathyroidism, hypercalcemia, hypokalemic metabolic alkalosis, nephrocalcinosis, and nephrogenic diabetes insipidus. The link between calcium and parathyroid hormone abnormalities in patients with SLC12A1 mutations is unclear; the cases described suggest an association between primary hyperparathyroidism and loss of function mutation of SLC12A1, which may result in an aberrant threshold of the calcium sensing receptor at the level of the kidney.
authors.affiliation: Center for Endocrinology, Diabetes and Metabolism, Division of Endocrinology, Children's Hospital Los Angeles, Los Angeles, CA, United States.
authors.forename: Sariya
authors.initials: S
authors.lastname: Wongsaengsak
authors.affiliation: Center for Endocrinology, Diabetes and Metabolism, Division of Endocrinology, Children's Hospital Los Angeles, Los Angeles, CA, United States.
authors.forename: Alaina P
authors.initials: AP
authors.lastname: Vidmar
authors.affiliation: Pediatric Endocrinology, Los Angeles County and University Medical Center University of Southern California, Los Angeles, California, United States.
authors.forename: Ananta
authors.initials: A
authors.lastname: Addala
authors.affiliation: Department of Pediatric Nephrology, Cedars-Sinai Medical Center, Los Angeles, CA, United States.
authors.forename: Elaine S
authors.initials: ES
authors.lastname: Kamil
authors.affiliation: Pediatric Endocrinology, Los Angeles County and University Medical Center University of Southern California, Los Angeles, California, United States; Keck School of Medicine of University of Southern California, Los Angeles, CA, United States.
authors.forename: Paola
authors.initials: P
authors.lastname: Sequeira
authors.affiliation: Pediatric Endocrinology, Kaiser Permanente Medical Center Los Angeles, Los Angeles, CA, United States.
authors.forename: Benjamin
authors.initials: B
authors.lastname: Fass
authors.affiliation: Center for Endocrinology, Diabetes and Metabolism, Division of Endocrinology, Children's Hospital Los Angeles, Los Angeles, CA, United States; Keck School of Medicine of University of Southern California, Los Angeles, CA, United States. Electronic address: dpisit@chla.usc.edu.
authors.forename: Pisit
authors.initials: P
authors.lastname: Pitukcheewanont
mesh_terms: D018500:Diabetes Insipidus, Nephrogenic / Q000235:genetics*; D005260:Female; D056726:Genetic Association Studies; D020022:Genetic Predisposition to Disease; D006801:Humans; D006934:Hypercalcemia / Q000235:genetics*; D049950:Hyperparathyroidism, Primary / Q000235:genetics*; D007223:Infant; D007231:Infant, Newborn; D008297:Male; D009154:Mutation / Q000235:genetics*; D009397:Nephrocalcinosis / Q000235:genetics*; D064466:Solute Carrier Family 12, Member 1 / Q000737:chemistry / Q000235:genetics*
chemical_list: C578714:SLC12A1 protein, human; D064466:Solute Carrier Family 12, Member 1
keywords: Antenatal Bartter's syndrome; Bartter's syndrome; Hypercalcemia; Hyperparathyroidism; SLC12A1 gene mutation