Exome Sequencing Identifies a Novel Homozygous Mutation in the Phosphate Transporter SLC34A1 in Hypophosphatemia and Nephrocalcinosis
Year: 2014
Type: article
Study design: Case Report
Abstract: CONTEXT: Two Argentinean siblings (a boy and a girl) from a nonconsanguineous family presented with hypercalcemia, hypercalciuria, hypophosphatemia, low parathyroid hormone (PTH), and nephrocalcinosis. OBJECTIVE: The goal of this study was to identify genetic causes of the clinical findings in the two siblings. DESIGN: Whole exome sequencing was performed to identify disease-causing mutations in the youngest sibling, and a candidate variant was screened in other family members by Sanger sequencing. In vitro experiments were conducted to determine the effects of the mutation that was identified. PATIENTS AND OTHER PARTICIPANTS: Affected siblings (2 y.o. female and 10 y.o male) and their parents were included in the study. Informed consent was obtained for genetic studies. RESULTS: A novel homozygous mutation in the gene encoding the renal sodium-dependent phosphate transporter SLC34A1 was identified in both siblings (c.1484G>A, p.Arg495His). In vitro studies showed that the p.Arg495His mutation resulted in decreased phosphate uptake when compared to wild-type SLC34A1. CONCLUSIONS: The homozygous G>A transition that results in the substitution of histidine for arginine at position 495 of the renal sodium-dependent phosphate transporter, SLC34A1, is involved in disease pathogenesis in these patients. Our report of the second family with two mutated SLC34A1 alleles expands the known phenotype of this rare condition.
DOI: 10.1210/jc.2014-1517
Language: English
Subfield: Nephrology
Field: Medicine
Domain: Health Sciences
Open Access status: bronze
Funders: Howard Hughes Medical Institute, National Institutes of Health, Intellectual and Developmental Disabilities Research Center, National Cancer Institute, National Institute of Allergy and Infectious Diseases, National Institute of Diabetes and Digestive and Kidney Diseases, National Institute of Child Health and Human Development, National Center for Research Resources, Eunice Kennedy Shriver National Institute of Child Health and Human Development
Awards: G1179207774, G1289049516, G1889080026, G2102565345, BD Biosciences Special Order LSRII, G3402682446, G3405376813, G3783386658, G4444814008, G5465708471, G6459864362, G6681871774, G7189771219, Pathogenesis of Novel Forms of Osteogenesis Imperfecta, G863484009, G8733582291, G9000096724, G9000198215, G9000240210, Baylor College of Medicine Cancer Center - Cancer Center Support Grant, G99424851
OpenAlex ID: W2069648131