title: A novel CASR mutation in a Tunisian FHH/NSHPT family associated with a mental retardation.
abstract: The calcium-sensing receptor (CASR), a plasma membrane G-protein coupled receptor, is expressed in parathyroid gland and kidney, and controls systemic calcium homeostasis. Inactivating CASR mutations have previously been identified in patients with familial hypocalciuric hypercalcemia (FHH) and neonatal severe hyperparathyroidism (NSHPT). The aim of the present study is to determine the underlying molecular defect of FHH/NSHPT disease in a consanguineous Tunisian family. Mutation screening was carried out using RFLP-PCR and direct sequencing. We found that the proband is homozygous for a novel 15 bp deletion in the exon 7 (c.1952_1966del) confirming the diagnosis of NSHPT. All the FHH members were found to be heterozygous for the novel detected mutation. The mutation, p.S651_L655del, leads to the deletion of 5 codons in the second trans-membrane domain of the CASR which is thought to be involved in the processes of ligand-induced signaling. This alteration was associated with the evidence of mental retardation in the FHH carriers and appears to be a novel inactivating mutation in the CASR gene. Our findings provide additional support for the implication of CASR gene in the FHH/NSHPT pathogenesis.
authors.affiliation: Research Unit 01/UR/08-14, Faculty of Medicine of Monastir, 5019 Monastir, Tunisia. sfarsana@yahoo.fr
authors.forename: Sana
authors.initials: S
authors.lastname: Sfar
authors.forename: Ahlem Afaya
authors.initials: AA
authors.lastname: Bzéouich
authors.forename: Emna
authors.initials: E
authors.lastname: Kerkeni
authors.forename: Sofiane
authors.initials: S
authors.lastname: Bouaziz
authors.forename: Mohamed Fadhel
authors.initials: MF
authors.lastname: Najjar
authors.forename: Lotfi
authors.initials: L
authors.lastname: Chouchane
authors.forename: Kamel
authors.initials: K
authors.lastname: Monastiri
mesh_terms: D001483:Base Sequence; D004252:DNA Mutational Analysis; D017931:DNA Primers / Q000235:genetics; D005260:Female; D056726:Genetic Association Studies; D020022:Genetic Predisposition to Disease / Q000235:genetics*; D006801:Humans; D006934:Hypercalcemia / Q000151:congenital* / Q000235:genetics; D006961:Hyperparathyroidism / Q000235:genetics*; D008607:Intellectual Disability / Q000235:genetics*; D008297:Male; D008969:Molecular Sequence Data; D010375:Pedigree; D016133:Polymerase Chain Reaction; D012150:Polymorphism, Restriction Fragment Length / Q000235:genetics; D044169:Receptors, Calcium-Sensing / Q000235:genetics*; D017384:Sequence Deletion / Q000235:genetics*; D014416:Tunisia
chemical_list: D017931:DNA Primers; D044169:Receptors, Calcium-Sensing