[Accuracy of lactase gene C/T-13910 polymorphism and hydrogen breath test in a gastroenterology outpatient clinic: a retrospective study]. / Laktózintolerancia: a laktázgén C/T-13910 polimorfizmusának és a hidrogénkilégzési teszt pontosságának retrospektív kiértékelése gasztroenterológiai szakrendelésen.

INTRODUCTION: Adult type hypolactasia is the most prevalent carbohydrate malabsorption. AIM: To assess the distribution of lactase gene C/T-13910 polymorphism and the accuracy and concordance of a genetic test and H(2) breath test in the diagnosis of adult type hypolactasia. METHOD: 496 patients with symptoms of lactose intolerance were enrolled in a retrospective study who underwent genetic test using TaqMan polymerase chain reaction and H(2) breath test. RESULTS: The prevalence of C/T-13910 genotypes was: CC 48.1%, TC: 40.5%, and TT: 11.4%. When the genetic test was taken as reference, the sensitivity of the breath test was 84.3%, with a specificity of 95.7%, a positive predictive value of 96.7% and negative predictive value of 80.4%. Conversely, the accuracy of genetic test was: sensitivity 96.6%, specificity 80.4%, positive predictive value 84.3% and negative predictive value 95.7%. The concordance value between the two tests (kappa index) was 0.78. The results were discordant in 11.1% of the cases. CONCLUSIONS: In symptomatic patients, the lactase non-persistence genotype CC occurred in almost half of the patients. Both the genetic and the breath tests are sufficiently accurate, with good predictive value and they can be used to set up the diagnosis. Discordant results should be carefully interpreted.

Rapid detection of sex chromosomal aneuploidies by QF-PCR: application in 200 men with severe oligozoospermia or azoospermia.

Klinefelter syndrome is the most common genetic cause of severe male factor infertility. Cytogenetic evaluation of metaphase chromosomes generally has a long turnaround time. We describe a reliable molecular genetic method that can be completed in 2 working days to identify the presence of any extra X chromosomes. The quantitative fluorescent (QF) 5-plex PCR includes the amplification of amelogenin, which is present on both sex chromosomes in a biallelic form, a polymorphic short tandem repeat (STR) on the pseudoautosomal region of X and Y (X22), two polymorphic X-specific STRs (DXS6803, DXS6809), and a Y-specific marker (SY134), in a single tube. The presence of an extra X chromosome is recognized either by a supernumerary peak or an increased peak area based on criteria we have developed. The application of the method on 200 patients resulted in the identification of 14 patients (7%) with Klinefelter syndrome or a variant form (2 SRY-positive 46,XX men), as well as an additional patient with 47,XYY karyotype. The QF-PCR method, along with Y chromosome microdeletion testing, can be used as a first-step genetic analysis in azoospermic or severely oligozoospermic patients for the rapid identification of sex chromosome aneuploidies.

Molecular and clinical analysis of patients with classic and Duarte galactosemia in western Hungary.

BACKGROUND: Classic galactosemia is an autosomal recessively inherited disorder caused by deficient activity of the enzyme galactose-1-phosphate uridyltransferase. The disorder can be detected by newborn screening and in Hungary the national screening program was launched in 1976 with two screening centers. The aim of this study was the molecular characterization of the genotypes and analysis of genotype-phenotype correlation among patients with classic or variant galactosemia. PATIENTS AND METHODS: DNA samples from 40 patients were analyzed by polymerase chain reaction followed by direct sequencing. RESULTS: 16 different sequence variations were identified, including two novel missense mutations (p.S297P, p.E146D). The two most common mutations were p. Q188R and p.K285N with allele frequencies of 45% and 31.2%, respectively. Clinical data were evaluated with respect to the genotypes found. CONCLUSIONS: The most serious clinical phenotypes in our population were associated with mutations p. Q188R, p.K285N, p.X380R, p.S297P, p.M142K, p.R.204X, p.Q169K and p.R407P, but manifestations depend on other genetic and environmental factors.

Mutations causing biotinidase deficiency in children ascertained by newborn screening in Western Hungary.

In Hungary the national newborn screening programme for the detection of biotinidase deficiency was launched in 1989. In this study, we determined the genotypes of all patients identified at the Budapest Screening Centre that covers half of the country. The incidence of the disorder in Western Hungary is about three times the worldwide incidence. Overall, 21 different mutations were identified in 49 patients, including four novel mutations. Ten mutations proved to be unique to the Hungarian population.