A novel mutation of the calcium-sensing receptor gene in a Greek family from Nisyros

Zapanti, Evaggelia; Polonifi, Aikaterini; Kokkinos, Michalis; Boutzios, George; Kassi, Georgia; Nasiri-Ansari, Νarjes; Kassi, Eva; Polyzos, Aris

doi:10.14310/horm.2002.1586

Cited by 2 publications

(3 citation statements)

References 15 publications

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“…As these mutations usually lead to a severely truncated protein, one would expect to result in a more severe phenotype. However, in most of the reported cases, patients feature typical findings with mildly elevated Ca 2+ (16,17) as was also observed in our case and her father as well as in the patients from Nisyros (11). Previous research has suggested that alterations caused by specific mutations depend on the location of the substituted amino acid in one of the critical regions for ligand binding, receptor trafficking, and signal transmission but not on the extend of the defect (13).…”

Section: Discussionsupporting

confidence: 83%

“…The genetic change was located in exon 4 of the CaSR gene and resulted in a new reading frame and theoretically, in a shorter CaSR protein. The same genetic change has been recently described in an adult patient with mild hypercalcemia and her two siblings originating from a Greek island (Nisyros) (11), however a functional assay was not performed to clarify the functional impact. No common ancestry is known between our patient and the patient from Nisyros.…”

Section: Discussionmentioning

confidence: 87%

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Identification and Functional Characterization of a Calcium-Sensing Receptor Mutation in an Infant with Familial Hypocalciuric Hypercalcemia

Papadopoulou

Gole²,

Melachroinou³

et al. 2016

Jcrpe

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Familial hypocalciuric hypercalcemia (FHH) is an autosomal dominant disorder, associated with inactivating mutations of the calcium-sensing receptor (CaSR). To evaluate the functional significance of a CaSR mutation, identified in a young infant who presented with hypercalcemia and hypocalciuria. The CaSR gene coding sequences were analyzed by polymerase chain reaction amplification and direct sequencing analysis. The mutation identified was introduced by site-directed mutagenesis into a wild-type (WT) CaSR plasmid, and human embryonic kidney 293 T cells were transfected with either the WT or mutant CaSR. The function of the mutated CaSR protein was analyzed by evaluating the free intracellular calcium [(Ca2+)i] response after challenge with extracellular calcium (Ca2+). We identified a heterozygous mutation c.772_773delGTinsA in exon 4 resulting in the substitution of amino acid valine (Val) with amino acid arginine (Arg) and the premature pause of the translation 46 amino acids later (Val258ArgfsTer47). Functional assay showed that cells transfected with the mutant CaSR had a significantly poorer response to extracellular Ca2+ stimulation compared with the WT. We have shown that the c.772_773delGTinsA mutation causes a significant alteration of CaSR function leading to features of FHH in an affected young infant since the first months of life.

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Section: Discussionsupporting

confidence: 83%

Section: Discussionmentioning

confidence: 87%

Identification and Functional Characterization of a Calcium-Sensing Receptor Mutation in an Infant with Familial Hypocalciuric Hypercalcemia

Papadopoulou

Gole²,

Melachroinou³

et al. 2016

Jcrpe

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show abstract

“…4 To date, more than 200 CaSR FHH-related mutations have been identified worldwide (online database available at http://www.casrdb.mcgill.ca). 5 Most mutations are missense and nonsense mutations, but deletions, insertions and splicing mutations have also been documented. The majority are localized in exons 3 and 4.…”

Section: Discussionmentioning

confidence: 99%

A novel mutation of the calcium-sensing receptor gene in a German subject with familial hypocalciuric hypercalcemia and primary hyperparathyroidism

Papadakis¹,

Meurer²,

Margariti³

et al. 2017

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oBjEcTIVE: The coexistence of familial hypocalciuric hypercalcemia (Fhh) and primary hyperparathyroidism (phpT) is extremely rare. genetic evidence has demonstrated a causal relationship between Fhh and the presence of inactivating mutations in the calcium-sensing receptor gene. METhoD: we herein report a 60-year-old german patient who was referred for hypercalcemia and increased pTh levels found incidentally during normal routine blood tests. rEsulTs: The patient underwent surgical exploration and the diagnosis of phpT was histologically confirmed. one week later, the follow-up blood tests revealed recurrent hypercalcemia, and the possibility of Fhh was reconsidered. genetic analysis was performed and revealed a novel heterozygous casr single missense mutation (Arg551gly) within the extracellular casr domain. conclusIon: we report a novel heterozygous missense inactivating mutation within the extracellular casr domain in a german subject with Fhh and histologically proven phpT.

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A novel mutation of the calcium-sensing receptor gene in a Greek family from Nisyros

Abstract: We hereby report the identification of a novel heterozygous loss-of-function mutation of the CASR gene in a Greek family from Nisyros island. Functional studies are needed to clarify the exact role of this mutation in CASR activity.

Cited by 2 publications

References 15 publications

Identification and Functional Characterization of a Calcium-Sensing Receptor Mutation in an Infant with Familial Hypocalciuric Hypercalcemia

Identification and Functional Characterization of a Calcium-Sensing Receptor Mutation in an Infant with Familial Hypocalciuric Hypercalcemia

A novel mutation of the calcium-sensing receptor gene in a German subject with familial hypocalciuric hypercalcemia and primary hyperparathyroidism

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