A novel CASR mutation in a Tunisian FHH/NSHPT family associated with a mental retardation

Sana Sfar, Ahlem Afaya Bzéouich, Emna Kerkeni, Sofiane Bouaziz, Mohamed Fadhel Najjar, Lotfi Chouchane, Kamel Monastiri

Research output: Contribution to journalArticle

4 Citations (Scopus)

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 ligandinduced 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.

Original languageEnglish
Pages (from-to)2395-2400
Number of pages6
JournalMolecular Biology Reports
Volume39
Issue number3
DOIs
Publication statusPublished - Mar 2012
Externally publishedYes

Fingerprint

Calcium-Sensing Receptors
Hyperparathyroidism
Intellectual Disability
Mutation
Parathyroid Glands
G-Protein-Coupled Receptors
Codon
Restriction Fragment Length Polymorphisms
Genes
Blood Proteins
Exons
Membrane Proteins
Homeostasis
Cell Membrane
Hypocalciuric hypercalcemia, familial, type 1
Calcium
Kidney
Polymerase Chain Reaction
Membranes

Keywords

  • Calcium-sensing receptor (CASR)
  • Familial hypocalciuric hypercalcemia
  • Mental retardation
  • Mutation analysis
  • Neonatal severe hyperparathyroidism (NSHPT)

ASJC Scopus subject areas

  • Genetics
  • Molecular Biology

Cite this

Sfar, S., Bzéouich, A. A., Kerkeni, E., Bouaziz, S., Najjar, M. F., Chouchane, L., & Monastiri, K. (2012). A novel CASR mutation in a Tunisian FHH/NSHPT family associated with a mental retardation. Molecular Biology Reports, 39(3), 2395-2400. https://doi.org/10.1007/s11033-011-0990-0

A novel CASR mutation in a Tunisian FHH/NSHPT family associated with a mental retardation. / Sfar, Sana; Bzéouich, Ahlem Afaya; Kerkeni, Emna; Bouaziz, Sofiane; Najjar, Mohamed Fadhel; Chouchane, Lotfi; Monastiri, Kamel.

In: Molecular Biology Reports, Vol. 39, No. 3, 03.2012, p. 2395-2400.

Research output: Contribution to journalArticle

Sfar, S, Bzéouich, AA, Kerkeni, E, Bouaziz, S, Najjar, MF, Chouchane, L & Monastiri, K 2012, 'A novel CASR mutation in a Tunisian FHH/NSHPT family associated with a mental retardation', Molecular Biology Reports, vol. 39, no. 3, pp. 2395-2400. https://doi.org/10.1007/s11033-011-0990-0
Sfar, Sana ; Bzéouich, Ahlem Afaya ; Kerkeni, Emna ; Bouaziz, Sofiane ; Najjar, Mohamed Fadhel ; Chouchane, Lotfi ; Monastiri, Kamel. / A novel CASR mutation in a Tunisian FHH/NSHPT family associated with a mental retardation. In: Molecular Biology Reports. 2012 ; Vol. 39, No. 3. pp. 2395-2400.
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