Przezierność karku powyżej 3,5mm u płodów z prawidłowym kariotypem - analiza wyników ciąż

Objectives: The objective was to study the outcomes of fetuses with increased nuchal translucency ≥3.5 mm and normal karyotype. Materials and methods: We performed a retrospective study on pregnancy outcomes and children development in 87 women with increased fetal nuchal translucency and normal karyotype who underwent chorionic villus sampling at our department. Mean observation period was 12 months after birth. Adverse pregnancy outcome was defined as miscarriage and intrauterine fetal demise, termination of pregnancy, structural defect, neonatal death, genetic syndrome and other major abnormalities. Results: The total incidence of adverse pregnancy outcome was 39.1% (n=34). The likelihood of an adverse pregnancy outcome, a major structural defect or major heart defect increased significantly with nuchal translucency (OR 3.77). 68 children (78.2%) were born alive. Nuchal translucency was significantly higher in newborns with adverse pregnancy outcome than in healthy children [4.1 mm vs. 5.7 mm; pCel pracy: Celem pracy była analiza rozwoju pre- i postnatalnego płodów ze zwiększoną przeziernością karku powyżej 3,5 mm i prawidłowym kariotypem. Materiał i metoda: Przeprowadzono retrospektywną analizę przebiegu ciąży i rozwoju dzieci u 87 pacjentek, u których wykonano biopsję trofoblastu w Pracowni USG I Kliniki Ginekologii i Położnictwa CMKP w SPSK im. prof.Orłowskiego z powodu przezierności karku płodu powyżej 3,5 mm (powyżej 99 percentyla) i otrzymano prawidłowy wynik kariotypu. Średni czas obserwacji po porodzie wynosił 12 miesięcy. Za niepomyślne zakończenie ciąży uznano poronienie i wewnątrzmaciczne obumarcie płodu, terminację ciąży, zgon dziecka po urodzeniu, występowanie ciężkiej wady anatomicznej, podejrzenie zespołu genetycznego i występowanie innych istotnych nieprawidłowości. Wyniki: W 34 (39,1%) przypadkach ciąża zakończyła się niepomyślnie. Ryzyko niepomyślnego wyniku ciąży, a w szczególności występowania ciężkiej wady anatomicznej oraz wady serca wzrastało wraz z wartością NT [OR 3,77]. W 68 przypadkach (78,2%) ciąża zakończyła się urodzeniem żywego noworodka. Wartość NT była istotnie statystycznie wyższa u żywo urodzonych dzieci, u których stwierdzono nieprawidłowości lub zgon po urodzeniu, niż u zdrowych noworodków [4,1 mm vs 5,7 mm;

Evaluation of the frequency of ADIPOQ c.45 T>G and ADIPOQ c.276 G>T polymorphisms in adiponectin coding gene in girls with anorexia nervosa

Introduction: Anorexia nervosa (AN) is a serious chronic psychosomatic disorder, the essence of which are attempts by the sufferer to obtain a slim silhouette by deliberate weight loss (restrictive diet, strenuous physical exercise, provoking vomiting). The aetiology of this disorder is multifactorial. Genetic factors that influence the predisposition to AN have been sought. A broad meta-analysis points to a strong genetic correlation between AN and insulin resistance. Adiponectin (ADIPO) increases insulin sensitivity. In our pilot study we demonstrated that the TT genotype in locus ADIPOQ c.276 G>T of the ADIPO gene and a higher concentration of ADIPO in blood serum occurred significantly more frequently in 68 girls suffering from AN than in 38 healthy girls. The objective of this study was to evaluate the frequency of the occurrence of ADIPOQ c.45 T>G and ADIPOQ c.276 G>T in the ADIPO gene in a larger cohort of girls with AN and healthy girls, as well as an analysis of correlations between variants of the aforementioned polymorphisms and the levels of ADIPO in blood serum. Material and methods: The study covered 472 girls (age: 11–19 years): 308 with the restrictive form of AN (AN) and 164 healthy girls (C). The level of ADIPO in blood serum was determined by means of the ELISA method on a Bio-Vendor, LLC (Asheville, North Carolina, USA). The DNA isolation was carried out by means of Genomic Mini AX BLOOD (SPIN). The PCR reaction was carried out in a ThermoCycle T100 thermocycler. 80–150 ng of the studied DNA and relevant F and R starters were added to the reaction mixture. The reaction products were subjected to digestion by restriction enzymes and separated on agarose gels (RFLP). Results: The distribution of genotypes in the polymorphic site ADP c.45 of the ADIPO gene and ADP c.276 was similar in both groups. In both groups the T allele was most frequent in locus ADIPOQ c.45 and the G allele in locus ADIPOQ c.276. In all the study subjects collectively (AN and C) a statistically significant negative correlation between the levels of ADIPO in blood serum on one hand and body weight (r = –0.46; p < 0.0001) and BMI (r = –0.67; p < 0.0001) on the other was demonstrated. Exclusively in the AN group a significant correlation between the level of ADIPO in blood and the distribution of TG, TT, and GG alleles in loci ADIPOQ c.45 and ADIPOQ c.276 was demonstrated (p = 0.0052 and p < 0.0001, respectively). Conclusions: The genotype in loci ADIPOQ c.45 and ADIPOQ c.276 of the ADIPO gene seems to have no effect on the predisposition to AN. Girls suffering from AN with the TT genotype in loci ADIPOQ c.45 and ADIPOQ c. 276 may demonstrate higher insulin sensitivity because they have significantly higher levels of ADIPO than girls suffering from AN with other genotypes. This may be suggestive of their better adaptation to the state of malnutrition, and it has a potential effect on treatment results

Evaluation of the frequency of RETN c.62G>A and RETN c.-180C>G polymorphisms in the resistin coding gene in girls with anorexia nervosa

Introduction: Anorexia nervosa (AN) is a serious psychosomatic syndrome, classified as an eating disorder. AN patients strive to lose weight below the normal limits defined for a specific age and height, achieving their goal even at the expense of extreme emaciation. AN has a multifactorial aetiology. Genetic factors are believed to be significant in the predisposition to the development of AN. In girls suffering from AN significantly lower levels of resistin (RES) in blood serum are observed as compared to healthy girls. These differences may lead to a thesis that functional genetic polymorphisms in RES coding genes can be responsible for this phenomenon. In our pilot study we demonstrated significant differences in the distribution of genotypes in the locus RETN c.-180C>G of the RES gene in 67 girls with AN and 38 healthy girls. It seems reasonable to compare the frequency of polymorphisms of RETN c.62G>A and RETN c.-180C>G in the RES gene in girls with AN and in healthy subjects in a bigger cohort and to analyse correlations between individual variants of the polymorphisms referred to above and the RES levels in blood plasma. Material and methods: The study covered 308 girls with the restrictive form of AN (AN) and 164 healthy girls (C) (aged 11–19 years). The RES levels in blood serum were determined by means of the ELISA method on a Bio-Vendor machine from LLC (Asheville, North Carolina, USA). The DNA isolation was carried out by means of Genomic Mini AX BLOOD (SPIN). The PCR reaction was carried out on a ThermoCycle T100 thermocycler. 80–150 ng of the studied DNA and relevant F and R starters were added to the reaction mixture. The reaction products were subjected to digestion by restriction enzymes and separated on agarose gels (RFLP). Results: The average RES level in blood serum in the AN group was significantly lower (p < 0.0001) than in the C group. The distribution of genotypes in the locus RETN c.62 of the RES gene was similar in both groups. A significant difference was demonstrated in the distribution of genotypes in the polymorphic site RETN c.-180 of the RES gene between AN and C (p = 0.0145) and in the distribution of the C and G alleles in the locus RETN c.-180 (p < 0.0001). The C allele occurred significantly more frequently than the G allele in the C group as compared to the AN group. In all the study subjects jointly (AN and C) a significant positive correlation between the blood RES levels on one hand and the body mass (r = 0.42; p < 0.0001) and BMI (r = 0.61; p< 0.0001) on the other was observed. There was no correlation between the concentration of RES in blood serum and the distribution of genotypes in the loci of the resistin gene referred to above. Conclusions: The CG genotype in the locus RETN c.-180 C>G of the RES gene may constitute one of the factors predisposing to the development of AN in girls. The genotype in the loci RETN c.62 G>A and RETN c.-180 C>G of the resistin gene has no influence on the levels of this hormone in blood in AN patients

Clinical manifestations of intermediate allele carriers in Huntington disease

Objective: There is controversy about the clinical consequences of intermediate alleles (IAs) in Huntington disease (HD). The main objective of this study was to establish the clinical manifestations of IA carriers for a prospective, international, European HD registry. Methods: We assessed a cohort of participants at risk with <36 CAG repeats of the huntingtin (HTT) gene. Outcome measures were the Unified Huntington's Disease Rating Scale (UHDRS) motor, cognitive, and behavior domains, Total Functional Capacity (TFC), and quality of life (Short Form-36 [SF-36]). This cohort was subdivided into IA carriers (27-35 CAG) and controls (<27 CAG) and younger vs older participants. IA carriers and controls were compared for sociodemographic, environmental, and outcome measures. We used regression analysis to estimate the association of age and CAG repeats on the UHDRS scores. Results: Of 12,190 participants, 657 (5.38%) with <36 CAG repeats were identified: 76 IA carriers (11.56%) and 581 controls (88.44%). After correcting for multiple comparisons, at baseline, we found no significant differences between IA carriers and controls for total UHDRS motor, SF-36, behavioral, cognitive, or TFC scores. However, older participants with IAs had higher chorea scores compared to controls (p 0.001). Linear regression analysis showed that aging was the most contributing factor to increased UHDRS motor scores (p 0.002). On the other hand, 1-year follow-up data analysis showed IA carriers had greater cognitive decline compared to controls (p 0.002). Conclusions: Although aging worsened the UHDRS scores independently of the genetic status, IAs might confer a late-onset abnormal motor and cognitive phenotype. These results might have important implications for genetic counseling. ClinicalTrials.gov identifier: NCT01590589

Reduced Cancer Incidence in Huntington's Disease: Analysis in the Registry Study

Background: People with Huntington's disease (HD) have been observed to have lower rates of cancers. Objective: To investigate the relationship between age of onset of HD, CAG repeat length, and cancer diagnosis. Methods: Data were obtained from the European Huntington's disease network REGISTRY study for 6540 subjects. Population cancer incidence was ascertained from the GLOBOCAN database to obtain standardised incidence ratios of cancers in the REGISTRY subjects. Results: 173/6528 HD REGISTRY subjects had had a cancer diagnosis. The age-standardised incidence rate of all cancers in the REGISTRY HD population was 0.26 (CI 0.22-0.30). Individual cancers showed a lower age-standardised incidence rate compared with the control population with prostate and colorectal cancers showing the lowest rates. There was no effect of CAG length on the likelihood of cancer, but a cancer diagnosis within the last year was associated with a greatly increased rate of HD onset (Hazard Ratio 18.94, p < 0.001). Conclusions: Cancer is less common than expected in the HD population, confirming previous reports. However, this does not appear to be related to CAG length in HTT. A recent diagnosis of cancer increases the risk of HD onset at any age, likely due to increased investigation following a cancer diagnosis

Clinical and genetic characteristics of late-onset Huntington's disease

Background: The frequency of late-onset Huntington's disease (&gt;59 years) is assumed to be low and the clinical course milder. However, previous literature on late-onset disease is scarce and inconclusive. Objective: Our aim is to study clinical characteristics of late-onset compared to common-onset HD patients in a large cohort of HD patients from the Registry database. Methods: Participants with late- and common-onset (30–50 years)were compared for first clinical symptoms, disease progression, CAG repeat size and family history. Participants with a missing CAG repeat size, a repeat size of ≤35 or a UHDRS motor score of ≤5 were excluded. Results: Of 6007 eligible participants, 687 had late-onset (11.4%) and 3216 (53.5%) common-onset HD. Late-onset (n = 577) had significantly more gait and balance problems as first symptom compared to common-onset (n = 2408) (P &lt;.001). Overall motor and cognitive performance (P &lt;.001) were worse, however only disease motor progression was slower (coefficient, −0.58; SE 0.16; P &lt;.001) compared to the common-onset group. Repeat size was significantly lower in the late-onset (n = 40.8; SD 1.6) compared to common-onset (n = 44.4; SD 2.8) (P &lt;.001). Fewer late-onset patients (n = 451) had a positive family history compared to common-onset (n = 2940) (P &lt;.001). Conclusions: Late-onset patients present more frequently with gait and balance problems as first symptom, and disease progression is not milder compared to common-onset HD patients apart from motor progression. The family history is likely to be negative, which might make diagnosing HD more difficult in this population. However, the balance and gait problems might be helpful in diagnosing HD in elderly patients