Omówienie problemu właściwej interpretacji kariotypu molekularnego przy próbie identyfikacji obserwowanych niezrównoważonych aberracji chromosomowych u pacjentów z niespecyficzną niepełnosprawnością intelektualną oraz zespołem mnogich wad wrodzonych

Ocena kariotypu pacjenta stanowi podstawę prawidłowej porady genetycznej mającej związek z podjętym leczeniem i/lub prewencją. W chwili obecnej laboratoria cytogenetyczne mają do dyspozycji ogromną liczbę metod diagnostycznych, w tym analizy kariotypu molekularnego oparteb na metodach CGH. Metody CGH pozwalają na wykrywanie zmian zdecydowanie mniejszych, w porównaniu z klasycznymi technikami cytogenetycznymi takimi jak metoda GTG. Niestety, brak możliwości bezpośredniej analizy chromosomów pacjenta może prowadzić do przekłamania podczas interpretacji wyniku. W poniższym opracowaniu przedstawiono dwa przypadki obrazujące najczęstsze problemy pojawiające się podczas i nterpretacji wyników kariotypu molekularnego metodą CGH.Evaluation of the patient's karyotype is the basis for proper genetic counseling, and thus also for a treatment or prevention to be taken. At present, cytogenetic laboratories have at their disposal a large number of diagnostic methods, including molecular karyotype analysis based on CGH procedures. The CGH methods allow to detect much smaller changes than conventional cytogenetic techniques such as a GTG method. Unfortunately, lack of direct analysis of patient's chromosomes may lead to a distortion in interpreting the result. The following paper presents two cases illustrating the most common problems in interpreting the results of molecular karyotyping using the CGH procedure

MTRNR2L12 : a candidate blood marker of early Alzheimer's disease-like dementia in adults with Down Syndrome

Morphological abnormalities observed typically in the brains of adults with Down syndrome are identical with those present in patients with Alzheimer’s disease. However, only some adults with Down syndrome suffer from early dementia, whereas others remain unaffected. We aimed to identify the genomic background responsible for this observation. We performed cognitive assessment and genome expression analysis of blood mononuclear cells in seniors with Down syndrome. Unaffected elderly patients and younger patients with severe cognitive disability or cognitive deterioration differed significantly with regard to the MTRNR2L12 gene. Our findings suggest the potential value of this gene as a blood marker of early dementia in individuals with Down syndrome

Ocena dynamiki mózgowego stężenia fenyloalaniny u pacjentów z fenyloketonurią

Background: Phenylketonuria (PKU) is the most common inborn error of metabolism in man. Brain phenylalanine kinetics can determine neurological treatment outcome in phenylketonuria. The aim of our study was to test a simplified magnetic resonance spectroscopy method for assessment of brain phenylalanine dynamics in PKU patients. Material/Methods: Brain phenylalanine concentration (measured by means of magnetic resonance spectroscopy) and blood phenylalanine concentrations changes occurring within 24 hours after oral phenylalanine loading were analyzed in 5 PKU patients. Results/Conclusions: The brain/blood phenylalanine ratio in 3 persons with normal intelligence was lower than in 2 with borderline intelligence or mild mental retardation. In our opinion the proposed method could be useful for assessment of brain phenylalanine dynamics in PKU patients

Impact of Hymenoptera venom allergy and the effects of specific venom immunotherapy on mast cell metabolites in sensitized children

Introduction and objective. Mast cells (MC) are effector cells during severe systemic reactions (SR) to Hymenoptera stings. Venom specific immunotherapy (VIT) is the treatment of choice for prevention of SR to stings. Tryptase and prostaglandin D2 metabolites (PGD2 ) are the markers of MC activation. The study design was to 1. compare baseline values of serum tryptase concentration (BST) and PGD2 metabolites in children with/without venom sensitization, 2. to evaluate an influence of rush VIT on MC markers in treated children. Materials and methods. Sensitized group: 25 children with SR to Hymenoptera sting. Control group: 19 healthy children. Active treatment: 5-day-rush-VIT. BST was evaluated by ImmunoCAP, PGD2 metabolites in blood and urine by GC-NICI-MS. Results. The baseline blood levels of MC markers were significantly higher, while urinary concentration of 9α,11β-PGF2 was significantly lower in the whole group of venom-sensitized children compared to controls. Severity of SR showed negative correlation with urinary PGD2 metabolites, while positive with plasma 9α,11β-PGF2 and BST concentration The highest sensitivity was obtained for plasma 9α,11β-PGF2 whereas the highest specificity for urinary PGD-M. Conclusions. In children with IgE-mediated SR to Hymenoptera stings, elevation of baseline values of PGD2 metabolites in blood is accompanied by decreased excretion of its urinary metabolites. Assessment of stable PGD2 metabolites might serve as an independent MC marker to identify allergic children. There is an association between urinary PGD2 metabolites and severity of the SR to Hymenoptera stings

Development of children's hymenoptera venom allergy quality of life scale (CHVAQoLS)

BACKGROUND: Venom allergy is a rare but life-threatening disease and may have a considerable impact on the health-related quality of life (HRQoL) of patients, especially children. This paper presents development of the HRQoL scale for children and adolescents with Hymenoptera venom allergy (HVA). METHODS: The study sample consisted of 71 children, born between 1992 and 2000, who presented with a history of insect sting reaction when referred for consultation in the allergy center of Polish-American Children’s Hospital, Krakow, Poland, during the period from 2000 to 2010. The initial pool of 60 items - divided into 6 domains - was prepared. The items with intercorrelations higher than 0.7 were removed from each domain and then principal component analysis was conducted for each domain separately, to provide a one-dimensional subscale for each domain. Reliability of the subscales was assessed using Cronbach alpha coefficient in terms of Classical Test Theory and with rho coefficient in terms of Item Response Theory. The multidimensionality of the scale was tested using multi-trait scaling. RESULTS: Three to four items from each domain were subsequently selected to constitute six subscales. Rho coefficients for all the subscales reached 0.8, similar results were achieved with the Cronbach alpha coefficients. Multi-trait method showed that the majority of the items indicated stronger correlations with their own subscales than with other subscales, which proves that our constructed subscales measure different dimensions of HRQoL. CONCLUSIONS: The presented scale comprises high validity and reliability subscales measuring six dimensions of HRQoL related to Hymenoptera venom allergy in children and adolescents. Such information may be useful in everyday clinical practice

Evaluation of Microfluidics-FISH method in prenatal diagnosis

Objectives: Classical cytogenetic analysis remains a gold standard in invasive prenatal diagnosis. Recently, Microfluidics¬-FISH, a novel method based on FISH, has been introduced. This integral approach allows to obtain result for common aneuploidies within the same day from a much smaller sample of the amniotic fluid. In this study we compare effectiveness of Microfluidics-FISH to classical karyotype and Rapid FISH. Material and methods: 52 samples of amniotic fluid were drawn from the pregnant women due to common indications. Cell cultures have been set up for classical cytogenetic analysis as well as amniotic cells have been loaded into the microchip of Microfluidics-FISH as well standard procedure of Rapid FISH was performed for evaluation of trisomy 21, 13, 18 chromosome and sex chromosomes numeric aberrations. Results: 9 samples out of 52 showed chromosomal aberrations in both FISH methods what was consistent with karyoty¬ping. One case of small supernumerary marker chromosome was detected only in the classical cytogenetic analysis. For the majority of cases turnaround time was shortest for Microfluidics-FISH and the average volume of sample was smallest. Microfluidics-FISH proved to be reliable and cost-effective rapid testing method of common aneuploidies. Recognizing, ho¬wever, limitations of methods based on FISH it cannot replace conventional karyotyping and be the sole method of diagnosis