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Stefano Mora

Publications and source records attributed to Stefano Mora.

23 records · Page 2Linked to original sources
PubMed2003

Establishment of peak bone mass.

Among the main areas of progress in osteoporosis research during the last decade or so are the general recognition that this condition, which is the cause of so much pain in the elderly population, has its antecedents in childhood and the identification of the structural basis accounting for much of the differences in bone strength among humans. Nevertheless, current understanding of the bone mineral accrual process is far from complete. The search for genes that regulate bone mass acquisition is ongoing, and current results are not sufficient to identify subjects at risk. However, there is solid evidence that BMD measurements can be helpful for the selection of subjects that presumably would benefit from preventive interventions. The questions regarding the type of preventive interventions, their magnitude, and duration remain unanswered. Carefully designed controlled trials are needed. Nevertheless, previous experience indicates that weight-bearing activity and possibly calcium supplements are beneficial if they are begun during childhood and preferably before the onset of puberty. Modification of unhealthy lifestyles and increments in exercise or calcium assumption are logical interventions that should be implemented to improve bone mass gains in all children and adolescents who are at risk of failing to achieve an optimal peak bone mass.

Adolescent↗
PubMed2002

Autosomal dominant hypocalcemia caused by a novel mutation in the loop 2 region of the human calcium receptor extracellular domain.

We report a novel missense mutation N124K in the extracellular calcium receptor (CaR) identified in two related subjects with the phenotypic features of autosomal dominant hypocalcemia (ADH). Expression of the N124K mutant receptor created by site-directed mutagenesis and transfected into HEK-293 cells was comparable with that of the wild-type (WT) receptor and two other mutant receptors N118K and L125P identified in subjects with ADH. Functional characterization by the extracellular Ca2+ ion ([Ca2+]0)-stimulated phosphoinositide (PI) hydrolysis in transfected HEK-293 cells showed that the N124K mutant receptor was left-shifted in Ca2+ sensitivity. This biochemical gain-of-function is comparable with that seen in other missense mutations of the CaR identified in subjects with ADH. We tested a series of missense substitutions (R, Q, E, and G) in addition to K for N124 and found that only the N124K mutation and to a much lesser extent N124R caused a left shift in Ca2+ sensitivity. Thus, a specific substitution, not merely a mutation of the N124 residue, is required for receptor activation. The N124K mutation is one of eight naturally occurring mutations in subjects with ADH identified in a short segment A116-C129 of the CaR extracellular domain (ECD). We present a hypothesis to explain receptor activation by mutations in this region based on the recently described three-dimensional structure of the related metabotropic glutamate type 1 receptor (mGluR1).

Adult↗
PubMedDate not supplied

Polymorphism of vitamin D receptor gene start codon in patients with calcium kidney stones.

BACKGROUND: A linkage has been detected between vitamin D receptor (VDR) locus and calcium kidney stone disease. In order to assess the eventual role of VDR gene start codon polymorphisms in stone production, we analyzed the genotype-phenotype association in a group of patients with calcium kidney stones. METHODS: One hundred and fifty-five patients were studied. VDR genotypes were characterized at the translation start site by restriction fragment length polymorphism analysis, using endonuclease FokI. Phenotypes of calcium-phosphate metabolism were compared in patients with different genotypes: strontium enteral absorption (used as a surrogate marker for calcium absorption), bone mineral density (BMD), calcium and phosphate excretion were measured. RESULTS: Genotype distribution was not different in hypercalciuric and normocalciuric stone formers. Enteral strontium absorption, calcium excretion and BMD did not vary with the patient's genotype. Serum concentrations of phosphate (p=0.022) and renal threshold for phosphate excretion (p=0.026) were lower in patients with genotype FF (homozygous for the absence of the FokI site) than in those with genotype ff (homozygous for the presence of the FokI site). The lower phosphatemia was confirmed in FF hypercalciuric patients, but not in normocalciuric ones. Serum concentrations of phosphate and calcitriol in the group of hypercalciuric patients were inversely correlated with the genotype FF. CONCLUSIONS: The FokI genotype does not appear to be involved in the causes of idiopathic hypercalciuria and kidney stones. Hypercalciuric patients with FF genotype may be a subgroup with low plasma concentrations of phosphate, predisposed to tubular leakage of phosphate.

Adult↗
PubMedDate not supplied

Autosomal dominant hypocalcemia with mild type 5 Bartter syndrome.

Type 5 Bartter syndrome has been recently defined as a Bartter syndrome due to the most activating mutations of the calcium-sensing receptor (CaSR). It has been attributed to the inhibition exerted by CaSR activity on sodium transport in the thick ascending limb of the loop of Henle (TALH). Two monozygotic twin sisters (T1 and T2) with autosomal dominant hypocalcemia (ADH) due to a nonconservative activating CaSR mutation in the extracellular domain (K29E) were studied. They developed a Bartter-like syndrome characterized by a mild phenotype: hypokalemia occurred only at the age of 22 years; it was corrected with small doses of oral potassium in one twin, while the other twin needed no potassium supplements to maintain borderline levels of plasma potassium; alkalosis was absent; plasma renin and aldosterone production were not markedly activated. Furthermore, the natriuretic response to furosemide, a inhibitor of sodium reabsorption in the TALH, was conserved in both twins. The K29E mutation was previously reported as one of the most activating mutations of the CaSR gene leading to a very marked increase in CaSR sensitivity to calcium ions. These findings confirm that Bartter syndrome is typically associated with ADH provided that the underlying mutation of CaSR is able to produce a conspicuous gain of function. However, the phenotype of type 5 Bartter syndrome may manifest with variable severity, not directly related with the in vitro potency of the CaSR activating mutation.

Adult↗