Mutations that inactivate one allele of the gene encoding the calcium sensing receptor (CaSR) cause autosomal dominant familial hypocalciuric hypercalcemia (FHH), whereas homozygous mutations cause neonatal severe hyperparathyroidism (SNHPT).
Objective: We describe the identification and biochemical characterization of a novel CASR gene mutation that caused SNHPT and FHH in a consanguineous kindred.
Design: The study design involved direct sequence analysis of the CaSR gene, clinical and biochemical analyses of the patient and his familys members.
Results: A novel inactivating mutation (p.S651_L655del) was identified in exon 7 of both alleles of the CASR in the proband, who presented with severe neonatal hyperparathyroidism. The probands parents and two siblings were heterozygous for the p.S651_L655del mutation consistent with autosomal dominant inheritance of FHH. All heterozygous subjects were hypercalcemic and hypercalciuric with normal PTH. The father and the two siblings had mental retardation with varied degree.
Conclusion: We identified a novel loss-of-function p.S651_L655del mutation in the CASR gene that exhibits FHH with mental retardation in heterozygote and SNHPT in homozygote. This study demonstrates the importance of biochemical and genetic testing for FHH in familys member of SNHPT to distinguish between de novo and inherited mutations of the CASR gene and questioned about the relationship between CASR gene mutation and cerebral development.
Prague, Czech Republic
24 - 28 Apr 2010
European Society of Endocrinology