Dong Li1, Lifeng Tian1, Cuiping Hou1, Cecilia E Kim1, Hakon Hakonarson1, Michael A Levine1. 1. The Center for Applied Genomics (D.L., L.T., C.H., C.E.K., H.H.), The Children's Hospital of Philadelphia, Philadelphia, Pennsylvania 19104; Department of Pediatrics (H.H., M.A.L.), University of Pennsylvania Perelman School of Medicine, Philadelphia, Pennsylvania 19104; and Division of Endocrinology and Diabetes and the Center for Bone Health (M.A.L.), The Children's Hospital of Philadelphia, Philadelphia, Pennsylvania 19104.
Abstract
CONTEXT: Primary hyperparathyroidism with hypercalciuria has not been described in the newborn period. OBJECTIVE: Our objectives are to identify the genetic basis for neonatal primary hyperparathyroidism in a family with 2 affected children. SUBJECTS: An African American boy presenting with mild neonatal primary hyperparathyroidism and hypercalciuria was evaluated at The Children's Hospital of Philadelphia. His older brother with neonatal primary hyperparathyroidism had died in infancy of multiple organ failure. METHODS: We collected clinical and biochemical data and performed exome sequencing analysis on DNA from the patient and his unaffected mother after negative genetic testing for known causes of primary hyperparathyroidism. RESULTS: Exome sequencing followed by Sanger sequencing disclosed 2 heterozygous mutations, c.1883C>A, p.(A628D) and c.2786_2787insC, p.(T931fsX10), in the SLC12A1 gene, which was previously implicated in antenatal type 1 Bartter syndrome. Sanger sequencing confirmed the 2 mutations in the proband and his deceased brother; both parents were heterozygous for different mutations and an unaffected sister was homozygous for wild-type alleles. CONCLUSIONS: These results demonstrate a previously unrecognized association between neonatal primary hyperparathyroidism and mutation of SLC12A1, the cause of antenatal Bartter syndrome type 1, and suggest that the loss of sodium-potassium-chloride cotransporter-2 cotransporter activity influences parathyroid gland function.
CONTEXT: Primary hyperparathyroidism with hypercalciuria has not been described in the newborn period. OBJECTIVE: Our objectives are to identify the genetic basis for neonatal primary hyperparathyroidism in a family with 2 affected children. SUBJECTS: An African American boy presenting with mild neonatal primary hyperparathyroidism and hypercalciuria was evaluated at The Children's Hospital of Philadelphia. His older brother with neonatal primary hyperparathyroidism had died in infancy of multiple organ failure. METHODS: We collected clinical and biochemical data and performed exome sequencing analysis on DNA from the patient and his unaffected mother after negative genetic testing for known causes of primary hyperparathyroidism. RESULTS: Exome sequencing followed by Sanger sequencing disclosed 2 heterozygous mutations, c.1883C>A, p.(A628D) and c.2786_2787insC, p.(T931fsX10), in the SLC12A1 gene, which was previously implicated in antenatal type 1 Bartter syndrome. Sanger sequencing confirmed the 2 mutations in the proband and his deceased brother; both parents were heterozygous for different mutations and an unaffected sister was homozygous for wild-type alleles. CONCLUSIONS: These results demonstrate a previously unrecognized association between neonatal primary hyperparathyroidism and mutation of SLC12A1, the cause of antenatal Bartter syndrome type 1, and suggest that the loss of sodium-potassium-chloride cotransporter-2 cotransporter activity influences parathyroid gland function.
Authors: Peter D Stenson; Edward V Ball; Matthew Mort; Andrew D Phillips; Jacqueline A Shiel; Nick S T Thomas; Shaun Abeysinghe; Michael Krawczak; David N Cooper Journal: Hum Mutat Date: 2003-06 Impact factor: 4.878
Authors: Bin Guan; James M Welch; Julie C Sapp; Hua Ling; Yulong Li; Jennifer J Johnston; Electron Kebebew; Leslie G Biesecker; William F Simonds; Stephen J Marx; Sunita K Agarwal Journal: Am J Hum Genet Date: 2016-10-13 Impact factor: 11.025
Authors: Colin Patrick Hawkes; Dong Li; Hakon Hakonarson; Kevin E Meyers; Kenneth E Thummel; Michael A Levine Journal: J Clin Endocrinol Metab Date: 2017-05-01 Impact factor: 5.958
Authors: Shana E McCormack; Dong Li; Yeon Joo Kim; Ji Young Lee; Soo-Hyun Kim; Robert Rapaport; Michael A Levine Journal: J Clin Endocrinol Metab Date: 2017-07-01 Impact factor: 5.958