Thirty-nine patients (10 women and 29 men) with a mean age 40±22.4 SEM years (range 7-66) underwent genetic test to evaluate the presence of GNA S1 gene mutations. For 4 of them, blood samples for genetic analysis from relatives were made available.

Table III – Subjects registered at the RIIP.

Developmental status of the patients was appropriate. The entire cohort of patients was biochemically characterized by serum evaluation of calcium, phosphorus, magnesium, alkaline phos­phatase, PTH, vitamin D (25 OH₂D₃ and 1-25 OH₂D₃), and or­gan- and non-organ specific antibodies. Thyroid function was evaluated by measurement of serum TSH, fT3 and fT4. A sample of urine was collected in order to evaluate the excretion of calci­um, phosphorus, magnesium deoxypiridinoline and cyclic AMP. In addition, routine exams were performed in all patients. Lumbar spine BMD (LS-BMD) was also measured by DEXA (Hologic QDR 4500). Electrorcardiogram, electromyography, ocular in­spection and skull X-ray and/or CT were performed in all patients. A new T>C polymorphic site of the GNAS1 gene was found in 7 patients and 4 relatives from different families indicated by A, B, C, D1, D2, D3, E1, F1, F2, G1, and G2 and it was not asso­ciated with modifications of restriction endonuclease recogni­tion sequences (Table IV). The clinical characteristics of pa­tients and of their first-degree relatives are summarized in Table IV. A patient affected (D1) and his sons (D2 and D3) showed the heterozygous T>C mutation and no mutations were found in the mother (D4). To buy cheap viagra pills online from a rx-approved online pharmacy

Table IV – Clinical and biochemical data of the hypocalcemic patients with GNAS1 gene mutations.

Patient D2 had a polymorphism at the exon 13 together with the T>C polymorphism at the in- tron 5. In addition, 13 patients had a polymorphism at the exon 5 of the GNAS1 gene previously described by Miric et al. (12). Two subjects were homozygous (Table IV). The clinical characteristic of 4 of the patients was available and reported in Table IV (subjects D2, L1, M1, M2, and N1). One patient (H1) affected by PHP-Ia had a missense mutation of the GNAS1 gene, characterized by Pro® Leu at the codon 115 in the exon 5, previously described by de Sanctis et al.. Three patients affected by APS 1 and their first-degree rela­tives underwent genetic test to evaluate the presence of AIRE gene mutations. Table V shows the characteristics of these pa­tients and relatives. The probands A1 and A2 had a homozy­gous mutation Thr®Met at the codon 16 in the exon 1 and a heterozygous mutation Prol®Leu at the codon 252 in the exon 6 already described in the literature. The mother (A3) had the heterozygous mutation Thr®Met at the codon 16 in the exon 1 and the father (A4) had both heterozygous mutation Thr®Met at the codon 16 in the exon 1 and the heterozygouscmutation Prol®Leu at the codon 252 in the exon 6. The B1 proband had a homozygous Arg®Stop Codon muta­tion in the exon 5 previously described by Scott et al.. The mother (B2), the father (B3), and the brother (B4) had the same heterozygous mutation.

Table V – Clinical characteristics of the subjects with AIRE gene mutations.

Conclusions

The recognition of the pathogenetic basis of hypocalcemic dis­orders is important for patient care, providing important clues for management, as subjects with activating CaSR mutations cannot be treated with vitamin D but would benefit most from PTH injections. Therapy of hypoparathyroid patients is not a primary outcome of the RIIP, however, the collection of pa­tient populations clinically and genetically characterized, repre­sents the necessary basis for the recognition of selected popu­lations for clinical trials. Finally, a careful genetic study of these patients will be useful in: a) precocious diagnosis of patients af­fected by a hypocalcemic disorder; b) prevention of complica­tions due to chronic hypocalcemia; and c) early treatment of associated disorders.

Figure 1 – Geographical distribution of the patients recorded at the RIIP. Of the total subjects registered at the RIIP 51% were from the South, 39% from the Center, and 10% form the North of Italy.