Endocrine Abstracts (2010) 22 P266

Familial hypercalciuric hypercalcemia and severe neonatal hyperparathyroidism: a clinico-biochemical and molecular characterization in a Tunisian family

Kamel Monastiri1,2, Ahlem Bziouch1, Sana Sfar1, Sofiane Bouaziz1, Fatma Zahra Chioukh2, Manel Bizid2, Hayet Ben Hamida2 & Fadhel Najjar3

1Research Unit 01/UR/08.14, Faculté de Médecine, Monastir, Tunisia; 2Department of Neonatology, Teaching Hospital Of Fattouma Bourguiba, Monastir, Tunisia; 3Departement of Biochemistry, Teaching Hospital of Fattouma Bourguiba, Monastir, Tunisia.

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 family’s 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 proband’s 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 family’s 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.

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