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Original research article INTRODUCTIONCystic fibrosis (CF), the most frequent life-shortening autosomal recessive disease in countries with a predominantly Caucasian population, is caused by mutations in the CF transmembrane conductance regulator (CFTR) gene. 1Because of the disease's severe clinical manifestations, the heavy burden of daily care, and the shortened life expectancy, carrier testing is routinely offered to relatives of CF patients. The CF carrier test may also be offered to individuals of reproductive age with no family history of CF. This carrier screening strategy has been recommended by the American College of Medical Genetics and Genomics 2 and by the American College of Obstetricians and Gynecologists, 3 whereas the European CF Society leaves the decision regarding its establishment up to individual countries. 4 Although no structured communitywide carrier screening has been implemented by any health jurisdiction, in the United States millions of carrier tests have been performed. 5 The CF carrier test is also offered to the general population in Israel 6 and in parts of Australia 7 and Italy. 8CF carrier screening has been found to be connected with a decrease in the annual birth prevalence of the disease in the United Kingdom, the United States, and Italy. 8-10Early diagnosis and management has been associated with better lung function and nutrition, as well as with reduced burden and cost of care. [11][12][13] To detect infants with CF soon after birth, newborn screening (NBS) has been implemented in most of Europe, North America, and Oceania, 14,15 and it is considered standard care.16,17 NBS-positive neonates undergo sweat chloride measurements to distinguish affected infants and healthy infants with false-positive results. In a subset of these infants, CF can be neither confirmed nor excluded. Several definitions have been suggested for this condition. In the United States it has been called "CFTR-related metabolic syndrome, " 18 and in Europe it is sometimes called "equivocal CF diagnosis" or "CF screening-positive inconclusive diagnosis. ". 19 In this article these situations are referred to as "uncertain CF. "The detection of false-positive results and of uncertain CF in infants is generally considered a secondary effect of the NBS system, and NBS programs are designed to minimize their number.15 It may be argued that the decrease in birth prevalence of CF associated with CF carrier screening 8 impairs the outcome of NBS by altering the proportions of CF, uncertain CF, and false-positive cases. 20This study was aimed at determining whether a negative correlation between carrier screening and birth prevalence of CF previously shown in northeastern Italy 8 is confirmed over a longer period, as well as whether it affects NBS practice. Purpose: We evaluated the effects of cystic fibrosis (CF) carrier screening on birth prevalence trends and newborn screening (NBS) efficiency by comparing two Italian regions; carrier screening was performed in one region (eastern region (ER)) and not in t...

The aim of our study was to investigate whether genetic variants in the hypocretin receptor 1 (HCRTR1) gene could modify the occurrence and the clinical features of migraine. Using a case–control strategy we genotyped 384 migraine patients and 259 controls for three SNPs in the HCRTR1 gene. Genotypic and allelic frequencies of the rs2271933 non-synonymous polymorphism resulted different (χ2 = 9.872, p = 0.007; χ2 = 8.108, p = 0.004) between migraineurs and controls. The carriage of the A allele was associated with an increased migraine risk (OR 1.42, 95% CI 1.11–1.81). When we divided the migraine patients into different subgroups, the difference reached the level of statistical significance only in migraine without aura. The different genotypes had no significant effect on the examined clinical characteristics of the disease. In conclusion, our data supports the hypothesis that the HCRTR1 gene could represent a genetic susceptibility factor for migraine without aura and suggests that the hypocretin system may have a role in the pathophysiology of migraine.

Following cystic fibrosis (CF) neonatal screening implementation, a high frequency of heterozygotes has been reported among neonates with elevated immunoreactive trypsinogen (IRT) and normal sweat chloride levels. We studied the relationship between normal IRT values and CF heterozygosity: 10,000 neonates were screened for CF by IRT measurement and tested for 40 CF mutations; the 294 carriers detected were coupled with newborns negative to the same genetic testing, and the two groups' IRT levels compared. Heterozygotes had higher IRT levels than their controls (mean 35.32 vs. 27.58 microg/L, P<0.001). Even within normal trypsinogen range, the probability of being a CF carrier increases with neonatal IRT concentration.