title: A novel homozygous deletion in the calcium-sensing receptor ligand-binding domain associated with neonatal severe hyperparathyroidism.
abstract: Neonatal severe hyperparathyroidism (NSHPT) is a life-threatening disorder usually caused by homozygous mutations occurring in the calcium-sensing receptor (CaR) gene. We examined an infant hospitalised with NSHPT for mutations in the CaR gene using heterozygous sequence analysis and confirmed this result by a restriction enzyme assay. Clinical management of this case, which was beset by other complications, involved control of the hypercalcemia and the effects of hyperparathyroidism by a combination of treatments prior to parathyroidectomy performed at 10 months. Mutational analysis demonstrated a homozygous 5 base-pair deletion in the CaR gene located at the 5' end of exon 4 which would result in a severely truncated, non-functional receptor with only the first 164 amino acids of the CaR followed by 23 amino acids of aberrant sequence. This is the first report of an out-of-frame deletion in the extracellular domain of the CaR associated with clinical disease.
authors.affiliation: Department of Endocrinology and Diabetes, Sir Charles Gairdner Hospital, Australia.
authors.forename: Bryan K
authors.initials: BK
authors.lastname: Ward
authors.forename: Fergus J
authors.initials: FJ
authors.lastname: Cameron
authors.forename: Aaron L
authors.initials: AL
authors.lastname: Magno
authors.forename: Ciara M
authors.initials: CM
authors.lastname: McDonnell
authors.forename: Bronwyn G A
authors.initials: BG
authors.lastname: Stuckey
authors.forename: Thomas
authors.initials: T
authors.lastname: Ratajczak
mesh_terms: D016368:Frameshift Mutation / Q000235:genetics*; D017353:Gene Deletion; D006801:Humans; D006961:Hyperparathyroidism / Q000097:blood / Q000151:congenital / Q000235:genetics* / Q000601:surgery; D007231:Infant, Newborn; D008297:Male; D010280:Parathyroid Glands / Q000601:surgery; D010281:Parathyroid Hormone / Q000097:blood; D010375:Pedigree; D017434:Protein Structure, Tertiary / Q000235:genetics; D044169:Receptors, Calcium-Sensing / Q000235:genetics*; D012720:Severity of Illness Index
chemical_list: D010281:Parathyroid Hormone; D044169:Receptors, Calcium-Sensing