[MODY 3 correlations between the genotype and clinical manifestations of diabetes]. / Correlazioni fra genotipo e manifestazioni cliniche del diabete in una famiglia affetta da MODY3.

We analyzed the mutations identified in a family affected by Maturity-Onset Diabetes of the Young (MODY3), and searched for correlations between the genotype and clinical manifestations of diabetes. In 4 of 9 subjects we have demonstrated a heterozygous missense mutation in hepatocyte nuclear factor 1 alfa (HNF1α). The missense mutation, caused by a G>A transition at nucleotide 815 of exon 4 (c.815G>A), resulted in the substitution of arginine with histidine at codon 272 (p.Arg272His). This mutation occurs in the DNA binding domain of HNF1α. Heterogenity of clinical characteristic in patients was evident. Variability in age of onset, presence of obesity and evolution time was present. In conclusion, clinical presentation of diabetes is otherwise atipical for the assumed etiology. Thus, the diagnosis of MODY should be raised in various clinical circumstances. Molecular diagnosis has important consequences in terms of prognosis, family screening, and therapy.

A new de novo mutation in the GCK gene causing MODY2.

Analysis of glucokinase (GCK) gene in a 15-year-old male identified a new frameshift mutation in exon 4 caused by a heterozygous guanine deletion at position 382 (c.382delG, p.E128Xfs). No mutation was detected in the parents. Polymorphic markers' study excluded false paternity indicating that c.382delG is a novel de novo mutation.

High recurrence of the R1006C NOTCH3 mutation in central Italian patients with cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL).

Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) is a heritable small-vessel disease caused by mutations in NOTCH3 gene and clinically characterized by recurrent ischemic strokes, migraine with aura, psychiatric symptoms, cognitive decline and dementia. Direct sequencing of NOTCH3 gene in 90 Italian patients of sixty-three unrelated families identified four heterozygous mutations (R141C and C144F in exon 4, G528C in exon 10 and R1006C in exon 19) in fifteen probands and sixteen relatives. We detected seventeen heterozygous/homozygous polymorphisms, four of them novel. Here we report the high recurrence of R1006C mutation in ten families all originate from a restricted area of central Italy, the town of Ascoli Piceno and same neighbour villages. We also developed a PCR-Restriction Fragment Length Polymorphism (RFLP) assay to analyze the R1006C mutation. Our findings might suggest, for this mutation, the presence of a common ancestor.

Novel mutations in GCK and HNF1A genes in Italian families with MODY phenotype.

Analysis of GCK and HNF1A genes in 32 MODY families identified three novel mutations: the missense mutation G170D and the deletion/insertion P432Xfs in GCK and the splicing mutation IVS4nt-1G>T, in HNF1A. For IVS4nt-1G>T the sequence analysis of RT-PCR products demonstrated exon skipping with the use of a cryptic splicing site.

[Minimally invasive surgery versus bilateral neck exploration for primary hyperparathyroidism: controlled prospective study. Role of intraoperative rapid parathyroid hormone assay and radiological preoperative detection of adenomas]. / Terapia chirurgica dell'iperparatiroidismo primitivo. Studio prospettico di confronto fra chirurgia tradizionale e chirurgia mininvasiva. ruolo della localizzazione radiologica preoperatoria e del dosaggio intraoperatorio del paratormone.

There is considerable controversy today concerning the most appropriate surgical approach for patients with primary hyperparathyroidism. The standard surgical approach involves a bilateral neck exploration. Minimally invasive surgery involves the removal of one parathyroid gland, pre-surgically localized with radiological techniques. Our purpose was to evaluate and compare the results of the 2 different surgical management in a follow-up period of observation. In our series of 15 consecutive female patients who underwent surgery, 5 (group I) underwent mini-invasive and 10 (group II) bilateral neck surgery. The first 10 were random selected to surgery; the successive 5 were assigned at group II. The normalization of calcemia was obtained in 100% of the women in group I and in 100% of the women in group II. Four patients of group I and two of group II had elevated PTH levels after surgery. Minimally invasive surgery for primary hyperparathyroidism depends on accurate preoperative localization of adenoma and the availability of IOPTHa for monitoring decrease of PTH concentration during surgery, while the IOPTHa is useless in case of conventional surgical operation. The data suggest that a focused unilateral surgical approach for hyperparathyroidism may underestimate the incidence of multiple-gland disease with persistent increase of PTH but not of calcemia. This technique may be useful for selected patients, older and without MEN syndrome.

Is there a future for clinical laboratories? Experience in the Marche Region, Italy.

The government of the Marche Region has approved an Act called the "Regional Health Plan" establishing rules for the organization and development of healthcare. The main aim of the general plan is to rationalize the activities of medical laboratories first by making up an inventory of existing facilities and tests performed, and by classifying laboratories on the basis of their specialization and the complexity of tests that they perform.Moreover, the possible role of point-of-care testing and the need for clinical advice by laboratory professionals has also been debated.