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 hyperparathyroidisin 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, nonfunctional 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.
Ward, B. K., Cameron, F. J., Magno, A. L., Mcdonnell, C. M., Stuckey, B. G. A., & Ratajczak, T. (2006). A novel Homozygous Deletion in the Calcium-Sensing Receptor Ligand-Binding Domain Associated with Neonatal Severe Hyperparathyroidism. JOURNAL OF PEDIATRIC ENDOCRINOLOGY & METABOLISM, 19, 93-100. https://doi.org/10.1515/JPEM.2006.19.1.93