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Background Antioxidant enzymes may play a significant role in the development of bronchopulmonary dysplasia (BPD). The aim of the study was to assess the relationship between the level of extracellular superoxide dismutase (SOD3) in the serum at days 1 and 7 of life and the risk of developing BPD. Methods The study comprised 103 neonates born before 32 weeks’ gestation with a birth weight of ≤1500 g. Results In the investigated group, the median serum SOD3 level at day 1 of life was 4.01 ng/mL [interquartile range (IQR) 2.59–5.09 ng/mL] and at day 7 of life 3.13 ng/mL (IQR 2.49–4.34 ng/mL). A statistically significant decrease in the serum SOD3 level was found in the first week of life, P Conclusion The study revealed a statistically significant decrease in the serum SOD3 level in the first week of life in very and extremely low birth weight infants born before 32 weeks of gestation. In the clinical setting, no relationship was observed between the level of SOD3 in serum and the risk of developing BPD.

Objectives: Recurrent reproductive loss (RPL) is a global health issue affecting a significant number of women. Approximately half of miscarriages have an unexplained etiology. Familial aggregation and twins studies prove that some cases of the RPL could have a genetic background. Recent evidences suggest that cytokines (e.g. IL-6, TNF alpha or TGF beta) and matrix metalloproteinases (MMP) are important for maintenance of pregnancy. Single gene polymorphisms (SNP), affecting these proteins production or their function may predispose to the loss of the pregnancy. The aim of this study was to evaluate the association between the following polymorphisms of IL6 (rs1800795), TNF (rs1800629), TGFB1 (rs1800471), MMP1 (rs1799750), MMP2 (rs2285053 and rs243865), MMP3 (rs35068180), MMP9 (rs3918242) and the recurrent pregnancy loss in polish population. Material and methods: Study subjects comprised of 67 patients with a history of recurrent pregnancy loss (≥ 2 miscarriages in history) and 75 controls. The distribution of genotypes for selected polymorphisms were determined by RFLP-PCR. Results: Maternal genotypes GG TNF, or 5A/5A MMP3 may be associated with the recurrent pregnancy loss. No association between the IL6, TGFB1, MMP1, MMP2, or MMP9 studied polymorphisms and the predisposition to miscarriage was found. Conclusions: This study demonstrated a possible association between rs1800629 TNF, rs35068180 MMP3 polymorphisms and recurrent pregnancy loss.

IntroductionCongenital hypogonadotropic hypogonadism results from a dysfunction of the hypothalamic-pituitary-gonadal axis, which is essential for the development and function of the reproductive system. It may be associated with anosmia, referred to as Kallmann syndrome, or a normal sense of smell. Numerous studies have proven that hypogonadotropic hypogonadism is not simply a monogenic Mendelian disease, but that more than one gene may be involved in its pathogenesis in a single patient. The oligogenic complex architecture underlying the disease is still largely unknown.Material and methodsTargeted next-generation sequencing (NGS) was used to screen for DNA variants in a cohort of 47 patients with congenital hypogonadotropic hypogonadism. The NGS panel consists of over 50 well-known and candidate genes, associated with hypogonadotropic state.ResultsHere we report the identification of new oligogenic variants in SPRY4/SEMA3A, SRA1/SEMA7A, CHD7/SEMA7A, CCDC141/POLR3B/POLR3B, and PROKR2/SPRY4/NSMF. These genes are known to contribute to the phenotype of hypogonadotropic hypogonadism, yet our results point to potential new “partners” underlying digenic and trigenic patterns.ConclusionsThe finding supports the importance of oligogenic inheritance and demonstrates the complexity of genetic architecture in hypogonadotropic hypogonadism. It also underlines the necessity for developing fine-tuned guidelines to provide a tool for adequate and precise sequence variant classification in non-Mendelian conditions.

This is a case report about very rare findings in 2nd half of pregnancy (after normal 1 trimester scan ) at 18th week of gestation fetal macrosomia was detected unrelated to maternal diabetes, and acceleration fetal growth later on with unusual cardiac abnormalities (fetal cardiomegaly, cardiomyopathy, partial abnormal venous connection ). Progressive features of congestive heart failure with polyhydramnios in a fetus with estimated 5500 g predicted a poor outcome and severe neonatal condition, which was presented and discussed with the parents to be. Casearean section was performed at 33rd weeks of gestation due to maternal dyscomfort, severe legs edema and her tachypnoe. Baby boy was delivered with birth weight of 5050g, Apgar 4 with mutiple tumors. Conservative care was introduced and neonated died on the 3rd day. Differential diagnosis was discussed with special attention to Costello syndrome however without proved by genetic make-up from neonatal blood.

Parabens are widely used as antimicrobial preservatives in cosmetics, pharmaceuticals, food and beverage processing due to their board spectrum of activity, inertness, and low cost. The study population consisted of 156 men under 45 years of age who attended the infertility clinic for diagnostic purposes with normal semen concentration of 15-300 mln/ml. Participants were interviewed and provided a semen sample. The parabens concentrations: ethyl paraben (EP), butyl paraben (BP), methyl paraben (MP), and iso-butyl paraben (iBuP) were analyzed in the urine using a validated gas chromatography ion-tap mass spectrometry method. The positive association was found between urinary level of BP and XY18 disomy (p = 0.045) and PP and disomy of chromosome 13 (p = 0.007). This is the first study to examine these relationships, and replication of our findings is needed before the association between parabens concentration in urine and aneuploidy can be fully defined. These findings may be of concern due to increased parabens use.

Hartsfield syndrome is a rare clinical entity characterized by holoprosencephaly and ectrodactyly with the variable feature of cleft lip/palate. In addition to these symptoms patients with Hartsfield syndrome can show developmental delay of variable severity, isolated hypogonadotropic hypogonadism, central diabetes insipidus, vertebral anomalies, eye anomalies, and cardiac malformations. Pathogenic variants in FGFR1 have been described to cause phenotypically different FGFR1-related disorders such as Hartsfield syndrome, hypogonadotropic hypogonadism with or without anosmia, Jackson–Weiss syndrome, osteoglophonic dysplasia, Pfeiffer syndrome, and trigonocephaly Type 1. Here, we report three patients with Hartsfield syndrome from two unrelated families. Exome sequencing revealed two siblings harboring a novel de novo heterozygous synonymous variant c.1029G>A, p.Ala343Ala causing a cryptic splice donor site in exon 8 of FGFR1 likely due to gonadal mosaicism in one parent. The third case was a sporadic patient with a novel de novo heterozygous missense variant c.1868A>G, p.(Asp623Gly).

Purpose This study aimed to investigate early-life folate serum concentrations in children with food, inhalant or mixed type allergy. The influence of folate levels on the FoxP 3 expression in Treg (regulatory T) cells in the studied children, taking into account the MTHFR (5,10-methylenetetrahydrofolate reductase) genotypes was also analyzed. Material and methods The study was performed in 83 allergic children (study group) and 49 healthy children (control group), aged 2–72 months. Medical history of each child was obtained and laboratory tests (serum folic acid concentrations and MTHFR C677T polymorphism) were carried out. The percentage of Treg cells was evaluated in almost a half of the examined subjects (48.5%). Results Significantly higher serum folate levels in the group of children with food allergy than in those with inhalant allergy was confirmed ( P = 0.037). In the study group the TT homozygotes were characterized by significantly lower folate concentrations than CC homozygotes ( P = 0.045). A negative correlation was demonstrated between the FoxP 3 expression in CD4 + CD25 high FoxP 3 + peripheral blood lymphocytes and serum folic acid concentrations. The correlation was more pronounced in the group of allergic children and it was statistically significant ( r = −0.339, P Conclusions The results of the study indicate a possibility of some effects of folate status on Treg cells, thus suggesting their potential role in the development and course of allergy in children.

In recent years, a trend toward a declining proportion of male births has been noted in several, but not all, industrialized countries. The underlying reason for the drop in the sex ratio is unclear, but one theory states that widespread environmental endocrine disrupting chemicals affecting the male reproductive system in a negative manner could be part of the explanation. The present study was designed to investigate whether the urinary phthalate, pyrethroids and polycyclic aromatic hydrocarbons metabolites concentrations were associated with sperm Y:X ratio. The study population consisted of 194 men aged under 45 years of age who attended infertility clinic in Lodz, Poland for diagnostic purposes with normal semen concentration of 20-300 mln/ml or with slight oligozoospermia (semen concentration of 15-20 mln/ml) (WHO, 1999). The Y:X ratio was assessed by fluorescent in situ hybridization. Urinary concentrations of 1-hydroxypyrene were measured by high performance liquid chromatography, phthalate metabolites were analyzed using a procedure based on the LC-MS/MS methods and metabolites of synthetic pyrethroids were assessed by gas chromatography ion-tap mass spectrometry method. After adjustment for potential confounders (past diseases, age, abstinence, smoking, alcohol consumption, sperm concentration, motility, morphology) 5OH MEHP, CDCCA to TDCCA and 1-OHP was negatively related to Y:X sperm chromosome ratio (p = 0.033, p

According to current diagnostic criteria, polycystic ovary syndrome (PCOS) is effective as a diagnosis of exclusion. Here, we present a case of a 31-year-old woman with a history of oligomenorrhoea and hirsutism, who, despite a “muscular” appearance and a normal body mass index (22.27 kg/m2), was found to have an extreme insulin resistance and diabetes accompanied by hyperandrogenism and polycystic ovaries. An autoimmune screen for possible latent autoimmune diabetes in adults was negative. She was subsequently found to have familial partial lipodystrophy (FPLD2, OMIM #151660) caused by an R482Q mutation in the LMNA gene encoding lamin A/C. This mutation results in arginine to glutamine substitution at the protein level, while phenotypically this condition presents with a loss of body fat, insulin resistance, dyslipidaemia, and other features mimicking PCOS. Interestingly her mother, with a history of myocardial infarction and diabetes at the age of 46 but no oligomenorrhoea, was also found to harbour the same mutation (LMNA R482Q). Conclusions: Our case highlights the importance of assessment of adipose tissue distribution, as well as a significance of assessment of glucose tolerance and insulin resistance in the differential diagnosis of PCOS. Furthermore, patients with atypical adipose tissue distribution should be referred for formal genetic testing. (Endokrynol Pol 2015; 66 (6): 550–554)

Introduction. In patients with Y-chromosome in the karyotype, partial gonadal dysgenesis and disorders of male reproductive sex organs development are usually resected in childhood because of the high risk of germ cell tumours (GCT). In patients with Y-chromosome, complete gonadal dysgenesis and female genitalia gonadectomy is performed markedly later. However, due to the relatively low number of adult patients with preserved dysgenetic gonads, the true risk of neoplasm is unknown. The aim of the study was to evaluate the prevalence of neoplasia in dysgenetic gonads of children and adults with Y-chromosome in a retrospective study. Material and methods. A review of medical documentation of 94 patients with disorders of sex development (DSD), Y-chromosome and gonadal dysgenesis (GD), aged 1.2–32 years (47 prepubertal, 1.2–10 years; 47 pubertal/adult, 13–32 years), was conducted. Serum levels of follicle-stimulating hormone (FSH), luteinizing hormone (LH) and testosterone were determined. Bilateral gonadectomy was performed in 73.4% of patients, and unilateral gonadectomy with biopsy of the contralateral gonad in 26.4%. All gonadal tissues were subjected to immunohistochemical evaluation with antibodies against PLAP and OCT3/4 (markers of malignant germ cells, but also foetal multipotent germ cells), while gonads of prepubertal patients were examined by c-KIT, as well. Results. Streak gonads were identified on both sides (complete GD) in 30.8%, a streak gonad on one side and an underdeveloped testis on the other (asymmetric GD) in 38.3%, and underdeveloped testicular structure on both sides (partial GD) in 30.8% of cases. Germ cell neoplasia was found in 53.2% of patients (51.1% in children, 55.3% in pubertal/adults). Invasive GCT were identified in 11.7% of cases, of which 90.9% were in pubertal/adult patients. Other neoplastic lesions included gonadoblastoma (16% prevalence) and testicular carcinoma in situ (25.5%). In younger patients FSH serum levels were increased in 81% of cases (mean 2.82 ± 2.18 IU/L), while LH in 58% (mean 1.82 ± 1.69 IU/L). Hypergonadotropic hypogonadism was diagnosed in most of the pubertal/ /adult patients (mean FSH 54.2 ± 23.3 IU/L, mean LH 21.7 ± 12.1 IU/L, mean testosterone 5.5 ± 4.5 nmol/L). Conclusions. Dysgenetic gonads in patients with Y chromosome have a high risk of germ cell neoplasia (ca. 50%). If they are preserved until puberty/early adulthood, they may develop overt, invasive GCT. The gonads also have poor hormonal activity (hypergonadotropic hypogonadism) in most of the pubertal/adult patients. Each of these cases must be considered individually and a decision to remove the gonad or not should be based on the comprehensive analysis of the phenotype by a multidisciplinary team of specialists in consultation with the patient and the parents. If dysgenetic gonads are not resected in childhood, these patients need careful ongoing follow-up examination, including biopsy and histopathological evaluation. (

The aim of the present study is to determine whether the environmental exposure to pyrethroids was associated with males sperm chromosome disomy. The study population consisted of 195 men who attended the infertility clinic for diagnostic purposes and who had normal semen concentration of 20–300 × 10 6 mL −1 or slight oligozoospermia (semen concentration of 15–20 × 10 6 mL −1 ) ( WHO, 1999 ). Participants were interviewed and provided a semen sample. The pyrethroids metabolites: 3-phenoxybenzoic acid (3PBA), cis -3-(2,2-dichlorovinyl)-2,2-dimethylcyclopropane carboxylic acid (CDCCA), trans -3-(2,2-dichlorovinyl)-2,2-dimethylcyclopropane carboxylic acid (TDCCA) and cis -2,2-dibromovinyl-2,2-dimethylcyclopropane-1-carboxylic acid (DBCA) were analysed in the urine using a validated gas chromatography ion-tap mass spectrometry method. Sperm aneuploidy was assessed using multicolor FISH (DNA probes specific for chromosomes X, Y, 18, 13, 21). Our results showed that CDCCA >50th percentile was associated with disomy of chromosome 18 ( p = 0.05) whereas the level of TDCCA in urine >50th percentile was related to XY disomy ( p = 0.04) and disomy of chromosome 21 ( p = 0.05). Urinary 3PBA level ⩽50 and >50 percentile was related to disomy of sex chromosomes: XY disomy ( p = 0.05 and p = 0.02 respectively), Y disomy ( p = 0.04 and 0.02 respectively), disomy of chromosome 21 ( p = 0.04 and p = 0.04 respectively) and total disomy ( p = 0.03 and p = 0.04 respectively). Additionally disomy of chromosome 18 was positively associated with urinary level of 3PBA >50 percentile ( p = 0.03). The results reported here are found that pyrethroids may be a sperm aneugens. These findings may be of concern due to increased pyrethroid use and prevalent human exposure.

Introduction Deletion of chromosome 22q11.2, which causes DiGeorge syndrome, is one of the most frequently diagnosed microdeletion syndromes in the human. It is characterised by a wide variety of symptoms. The main symptoms consist of congenital heart diseases, particularly conotruncal malformations, characteristic facial dysmorphism, palatal abnormalities, an immune deficiency and hypocalcemia. We present phenotypical analysis of 15 patients with DiGeorge syndrome without structural heart disease. A diagnosis of DiGeorge syndrome was confirmed by Multiplex Ligation-dependent Probe Amplification (MLPA) and Fluorescent in situ Hybridization (FISH) with a specific probe. Results FISH method was used in 10 patients in genetic diagnosis of microdeletion 22q11.2 syndrome, and MLPA method confirmed that FISH analysis was used in 5 patients. None of the patient exhibited heart disease in an ultrasound examination. Developmental delay (13/15), delay in emergence of language (8/15), palatal abnormalities (10/15) and frequent infections (11/15) were observed. All the patients presented characteristic facial features. Conclusions It is difficult to diagnose DiGeorge syndrome in patients who do not present heart disease. In such cases careful phenotypical analysis and microdeletions screening with MLPA method may be helpful to make a diagnosis. To establish appropriate therapy and further clinical evaluation exact and early diagnosis is crucial. There lacks diagnostic guidelines for patients with unexplained developmental delay and/or developmental malformations.

Possible reproductive toxicants such as occupational factors may affect the normal disjunction of chromosomes during meiosis, thereby altering the number of chromosomes in sperm nuclei. The purpose of the present analysis was to determine whether exposure to occupational factors existing in a contemporary work setting affected sperm aneuploidy. The study population consisted of 212 men who attended the infertility clinic for diagnostic purposes. The men either had a normal semen concentration of 20-300 million/ml or slight oligozoospermia (semen concentration of 15-20 million/ml) ( WHO 1999 ). All participants were interviewed and provided a semen sample. Sperm aneuploidy was assessed using multicolor FISH. After adjustment for potential confounders, positive associations were found between disomy XY18, 18, and sex chromosome disomy and exposure to mechanical vibrations (p = 0.03, p = 0.04, p = 0.03, respectively). In addition, sitting for more than 6 h at work increased X and Y disomy (p = 0.03, p = 0.04, respectively). To the best of our knowledge, this is the first study to show a significant effect of occupational factors on sperm aneuploidy. As such, the results need to be confirmed in larger studies.

The present study was designed to address the hypothesis that exposure to specific air pollutants may impact human sperm Y:X chromosome ratio. The study population consisted of 195 men who were attending an infertility clinic for diagnostic purposes and who had normal semen concentration of 15-300 mln/ml (WHO, 2010). Participants represented a subset of men in a multicenter parent study conducted in Poland to evaluate environmental factors and male fertility. Participants were interviewed and provided a semen sample. The Y:X ratio was assessed by fluorescent in situ hybridization (FISH). Air quality data were obtained from the AirBase database. In multivariate analysis the significant reduction was observed in the proportion of Y/X chromosome bearing sperm and exposure to particulate matter >10 μm in aerodynamic diameter PM10( p = .009) and particulate matter

The causes of the chromosome abnormalities have been studied for decades. It has been suggested that exposure to various environmental agents can induce chromosomal abnormalities in germ cells. This study was designed to address the hypothesis that exposure to specific air pollutants increases sperm disomy. The study population consisted of 212 men who were attending an infertility clinic for diagnostic purposes. They represented a subset of men in a multicenter parent study conducted in Poland to evaluate environmental factors and male fertility. Sperm aneuploidy for chromosomes 13, 18, 21, X, and Y was assessed using multicolor fluorescence in situ hybridization. Air quality data were obtained from the AirBase database. After adjusting for age, smoking, alcohol consumption, temperature (90 days), season, past diseases, abstinence interval, distance from the monitoring station, concentration, motility and morphology, positive associations were observed between exposure to PM2.5 and disomy Y (P = 0.001), sex chromosome disomy (P = 0.05) and disomy 21 (P = 0.03). Exposure to PM10 was associated with disomy 21 (P = 0.02). Conversely, exposure to ozone, CO, SO2, and NOx did not affect sperm aneuploidy. A separate analysis conducted among men who were nonsmokers (n = 117) showed that the relationship between PM2.5 and disomy Y and disomy 21 remained significant (P = 0.01, P = 0.05, respectively). The present findings indicate that exposure to air pollution induces sperm aneuploidy.

The aim of the study was to assess the association of phthalate metabolites levels in urine with semen parameters (sperm concentration, motility, morphology, CASA parameters), sperm chromatin structure, sperm aneuploidy and reproductive hormones. The study population consisted of 269 men who were attending an infertility clinic and had normal semen concentration (20-300mln/ml) or slight oligozoospermia (15-20mln/ml). Participants were interviewed and provided a semen sample. The phthalate metabolites were analysed in the urine using a procedure based on the LC-MS/MS method. Urinary phthalate metabolites levels were significantly associated with a decrease in sperm motility (5OH MEHP, MEHP, MINP), CASA parameters (MBP), testosterone level (MEHP) and an increase sperm DNA damage (MBP) and sperm aneuploidy (MBzP, MBP, MEHP, MEP). In view of the importance of human reproductive health and the widespread usage of phthalates, it is important to further investigate these correlations.

In recent years, a trend toward a declining proportion of male births has been noted in several, but not all, industrialised countries. The underlying reason for the drop in the sex ratio is unclear, but one theory states that widespread environmental endocrine disrupting chemicals affecting the male reproductive system in a negative manner could be part of the explanation. The present study was designed to investigate whether the urinary phthalate, pyrethroids and polycyclic aromatic hydrocarbons metabolites concentrations were associated with sperm Y:X ratio. The study population consisted of 194 men aged under 45 years of age who attended infertility clinic in Lodz, Poland for diagnostic purposes with normal semen concentration of 20–300 mln/ml or with slight oligozoospermia (semen concentration of 15–20 mln/ml) (WHO, 1999). The Y:X ratio was assessed by fluorescent in situ hybridization. Urinary concentrations of 1-hydroxypyrene were measured by high performance liquid chromatography, phthalate metabolites were analysed using a procedure based on the LC-MS/MS methods and metabolites of synthetic pyrethroids were assessed by gas chromatography ion-tap mass spectrometry method. After adjustment for potential confounders (past diseases, age, abstinence, smoking, alcohol consumption, sperm concentration, motility, morphology) 5 OH MEHP, CDCCA to TDCCA and 1-OHP was negatively related to Y:X sperm chromosome ratio (p = 0.033, p As this is the first study to elucidate the association between the level of metabolites of widespread environmental endocrine disrupting chemicals (phthalates, synthetic pyrethroids, polycyclic aromatic hydrocarbons) on sex chromosome ratio in sperm therefore, these findings require further replication in other populations.

Summary Background: Mast cells, owing to diversity of secreted mediators, play a crucial role in the regulation of inflammatory response. Together with basophils, mast cells constitute a central pathogenetic element of anaphylactic (IgE-dependent) and anaphylactoid (IgE-independent) reactions. In severe cases, generalized degranulation of mast cells may cause symptoms of anaphylactic shock. The influence of the classical, iodine-based contrast media on mastocyte degranulation has been fully described. Our objective was to determine the influence of the gadolinium-based MRI contrast media on histamine release from mast cells and to compare the activity of ionic and non-ionic preparations of contrast media. Material/Methods: To determine the intensity of mast cell degranulation, we used an experimental model based on mastocytes isolated from rat peritoneal fluid. Purified suspensions of mast cells were incubated with various concentrations of Gd-DTPA and Gd-DTPA-BMA, and solutions of PEG 600 which served as a non-toxic osmotic stimulus. The intensity of mast cell activation was presented as mean percentage of histamine released from cells after incubation. Results/Conclusions: The obtained results demonstrate that both ionic and non-ionic preparations of the MRI contrast media are able to induce mast cell degranulation in vitro. It was also proved that the non-ionic MRI contrast media stimulate mast cells markedly more weakly than ionic contrast media at identical concentration. The aforementioned results may suggest a more profitable safety profile of the non-ionic contrast preparations. We may also conclude that triggering of mast cell degranulation after incubation with the solutions of MRI contrast media results from non-specific osmotic stimulation and direct toxicity of free ionic residues.

This paper contains a joint position of the Polish Gynecological Society and Polish Human Genetics Society on the cell-free fetal DNA testing in prenatal diagnosis. We present situations where the cell-free fetal DNA testing should be applied and cases in which performing of the test is not useful. We indicate what diagnostic steps should be performed before the test and how the test results should be interpreted and followed.

We report on two siblings with a severe neonatal form of spondylometaphyseal dysplasia (SMD). Similar cases have been reported in four publications. Analysis of pedigree data from the original and present families suggests an autosomal recessive mode of inheritance, although parental gonadal mosaicism is also possible. The similarities in the phenotype between our patients and spondyloepimetaphyseal dysplasia congenita (SEMDC) and spondyloepimetaphyseal dysplasia Strudwick (SEMDS) type, indicated that these patients could have a defect in the COL2A1 gene. Molecular analysis of genomic DNA of these patients excluded this gene. Another potential candidate gene PTHR1, was also analyzed in the selected regions and no mutation was found. This gene is probably causative in the Jansen type of SMD, which shares some phenotypic features with the siblings whom we documented. Our results indicate that a new candidate gene for the reported form of SMD should be sought.

Robertsonian translocations 13/14 are the most common chromosome rearrangements in humans. However, most studies aimed at determining risk figures are more than 20 years old. Their results are often contradictory regarding important topics in genetic counseling such as infertility and unfavorable pregnancy outcomes. Here, we present a study on a sample of 101 previously unreported pedigrees of der(13;14)(q10;q10). In order to minimize problems of partial ascertainment, we included families with a wide range of reasons of ascertainment such as birth of a child with congenital anomalies, prenatal diagnosis due to maternal age, fertility problems and recurrent pregnancy loss. No evidence of increased infertility rates of female and male carriers was found. The detected miscarriage frequency of female carriers was higher than previously reported (27.6 +/- 4.0% of all spontaneous pregnancies). This may be explained by an over-correction of earlier studies, which excluded all unkaryotyped miscarriages. In three out of 42 amniocenteses, translocation trisomies 13 were diagnosed (7.1 +/- 4.0% of all amniocenteses). The frequency of stillbirths was 3.3 +/- 1.6% for female carriers and 1.4 +/- 1.4% for male carriers. A low risk for the live birth of translocation trisomy 13 children was confirmed since no live born children with trisomy 13 or Pätau syndrome were detected in the ascertainment-corrected sample.

The regulatory influence of the pineal gland on superficial wound healing and collagen content is documented. The aim of the present study was to determine whether the pineal gland and its secretory product melatonin regulate collagen accumulation in the scar of the infarcted heart and to explain the mechanisms of its action. To induce myocardial infarction in rats the left coronary artery was ligated. Metoprolol at the dose of 0.2 mg/100 g body weight (b.w.) was injected intraperitoneally to inhibit melatonin secretion. Pinealectomy was performed on some animals. For the in vitro study, cells were isolated from the heart scar and cultured in Dulbecco's modified Eagle medium with 3% fetal calf serum and antibiotics. Collagen content was evaluated as hydroxyproline content according to the Woessner method. Melatonin subcutaneously injected into the rats at the doses of 30 microg/100 g or 60 microg/100 g b.w. increased collagen accumulation in the heart scar. The doses of 3 microg/100 g b.w. and 300 microg/100 g b.w. were not effective. Surgical and pharmacological pinealectomies had opposite effects and reduced collagen content in the scar. However, melatonin administration (60 microg/100 g b.w.) to pinealectomized rats reversed the effect of pinealectomy and normalized collagen levels in heart after infarction. Cells isolated from the heart scar were identified as myofibroblasts. Melatonin (10(-7)-10(-8) m) increased collagen accumulation in the cultures. Collagen accumulation in the scar of the infarcted heart is regulated by melatonin and it exerts effects directly on the myofibroblasts of the infarcted area. Therefore, melatonin-induced collagen accumulation in the infarcted heart could be considered as the event improving the tensile strength of the scar and retarding the development of complications.

Cu/Zn superoxide dismutase (SOD-1) (E.C.1.15.1.1.) activity was estimated in children with regular trisomy 21-Down syndrome as well as in cases of translocation and mosaic trisomy 21, as identified by the GTG, CBG and RHG banding techniques. SOD-1 activity was found to be increased in all examined cases except trisomy 21 mosaicism. These findings provide further proof of the gene dosage theory and additional biochemical evidence for the triplicate existence of the SOD-1 gene localized on chromosome 21

Objectives To determine whether dietary patterns are associated with the frequency of sperm aneuploidy in a human sperm. It was shown that the role of nutrition, especially dietary pattern, remains unexamined as a risk factor in sperm aneuploidy. In contrast to the traditional analytical approach used in nutritional epidemiology, dietary pattern analysis considers overall diet rather than individual nutrients or foods. Methods The study population consisted of 212 men who were attending an infertility clinic for diagnostic purposes and who had semen concentration of ≥15 (106/ml) (World Health Organization, 2010). Sperm aneuploidy was assessed using multicolor fluorescent in situ hybridization (DNA probes specific for chromosomes 13, 18, 21, X, Y). Diet was assessed via food frequency questionnaire and dietary patterns were identified by factor analysis. Men were classified into 3 groups according to scores of each dietary pattern: Western, Mixed, Prudent. Results In multivariate analysis, Prudent dietary pattern characterized by high intakes of fish, chicken, fruit, cruciferous vegetables, tomatoes, leafy green vegetables, legumes, and whole grains decreases disomy of chromosomes XX and 21 (P = .01 and P = .005) compared with Western dietary pattern characterized by high intakes of red and processed meat, butter, high fat dairy, refined grains, pizza, snacks, high-energy drinks, and sweets. Conclusion Higher consumption of Prudent dietary pattern was associated with decreased frequencies of sperm disomy. As this is the first study to analyze the relation of diet and the frequency of sperm aneuploidy, our findings merit further studies, in other populations.

According to current diagnostic criteria, polycystic ovary syndrome (PCOS) is effective as a diagnosis of exclusion. Here, we present a case of a 31-year-old woman with a history of oligomenorrhoea and hirsutism, who, despite a "muscular" appearance and a normal body mass index (22.27 kg/m2), was found to have an extreme insulin resistance and diabetes accompanied by hyperandrogenism and polycystic ovaries. An autoimmune screen for possible latent autoimmune diabetes in adults was negative. She was subsequently found to have familial partial lipodystrophy (FPLD2, OMIM #151660) caused by an R482Q mutation in the LMNA gene encoding lamin A/C. This mutation results in arginine to glutamine substitution at the protein level, while phenotypically this condition presents with a loss of body fat, insulin resistance, dyslipidaemia, and other features mimicking PCOS. Interestingly her mother, with a history of myocardial infarction and diabetes at the age of 46 but no oligomenorrhoea, was also found to harbour the same mutation (LMNA R482Q).Our case highlights the importance of assessment of adipose tissue distribution, as well as a significance of assessment of glucose tolerance and insulin resistance in the differential diagnosis of PCOS. Furthermore, patients with atypical adipose tissue distribution should be referred for formal genetic testing.

Bardet Biedl Syndrome (BBS) is a rare, genetically determined syndrome which can result from a mutation in one of 19 known genes (often called BBS complex), which play a vital role in building structures and cell functions of cilia. Phenotypic symptoms of the syndrome usually progress in the first decade of life, however, they are characterized by a high diversity which makes their diagnosis difficult, especially in the early stage of life. The diagnosis is most frequently based on clinical symptoms and established in late childhood or adult life. BBS is a disorder of the non-motile cilia, which play the role of antennae receiving and transmitting sensory signals to photoreceptors of the retina, hearing cells or olfactory cells. Clinical symptoms of the disorders affecting these structures are: retinal pigmentary degeneration, polydactyly, learning difficulties, and formation of kidney, liver and pancreas cysts. The inheritance mode of BBS is in 80% autosomal recessive, which is connected with both parents carrying a mutated allele, and usually only giving birth to a symptomatic child defines a family as being at genetic risk, whith 25% risk of having another child with the disease and 50% of having offspring that are asymptomatic carriers For families with an identified mutation there exists a possibility of conducting prenatal or preimplementation genetic diagnosis in subsequent pregnancies The article presents a case of a patient in whom prenatal ultrasonography and subsequent clinical trials in post-natal period resulted in a Bardet-Biedl syndrome diagnosis, which was later confirmed through molecular tests.

The causes of the chromosome abnormalities have been studied for decades. It has been suggested that exposure to various environmental agents can induce chromosomal abnormalities in germ cells. This study was designed to address the hypothesis that exposure to specific air pollutants increases sperm disomy. The study population consisted of 212 men who were attending an infertility clinic for diagnostic purposes. They represented a subset of men in a multicenter parent study conducted in Poland to evaluate environmental factors and male fertility. Sperm aneuploidy for chromosomes 13, 18, 21, X, and Y was assessed using multicolor fluorescence in situ hybridization. Air quality data were obtained from the AirBase database. After adjusting for age, smoking, alcohol consumption, temperature (90 days), season, past diseases, abstinence interval, distance from the monitoring station, concentration, motility and morphology, positive associations were observed between exposure to PM2.5 and disomy Y (P = 0.001), sex chromosome disomy (P = 0.05) and disomy 21 (P = 0.03). Exposure to PM10 was associated with disomy 21 (P = 0.02). Conversely, exposure to ozone, CO, SO2, and NOx did not affect sperm aneuploidy. A separate analysis conducted among men who were nonsmokers (n = 117) showed that the relationship between PM2.5 and disomy Y and disomy 21 remained significant (P = 0.01, P = 0.05, respectively). The present findings indicate that exposure to air pollution induces sperm aneuploidy.

We have performed cytogenetic and molecular analyses of 45,X mosaics involving structurally abnormal Y chromosomes. Karyotypes were performed by standard cytogenetic methods and, in some cases, by fluorescence in situ hybridization, to distinguish monocentric and dicentric chromosomes. In addition, the deletions of Yq have been mapped using Southern blotting and polymerase chain reaction analysis. This paper provides additional information on the analysis of Y chromosome aberrations, and suggests that the stability of the Y chromosome in these instances is related to the site of the break point on Yq.

Kallmann syndrome type 1 (KS1) is a heterogeneous disorder where hypogonadotropic hypogonadism (HH) associated with an impaired sense of smell is observed. The aim of this study was to investigate the usefulness of the multiplex ligation-dependent probe amplification (MLPA) technique for differential diagnosis in comparison with molecular cytogenetics - fluorescence in situ hybridisation (FISH) or traditional PCR analysis and propose a diagnostic approach for patients with KS.Karyotype and PCR analysis in two related patients and other family members were performed, followed by MLPA dosage sensitive analysis.In the proband and his maternal uncle, the PCR allowed the detection of a large deletion within the KAL1 gene, from exon 4 to 14 (c.469-?_6314+?del). The deletion was also diagnosed in three female carriers in the presented family. These results were proved by the MLPA technique. Moreover, we traced the presence of the region located downstream and upstream to the KAL1 gene on Xq22.32. However, FISH analysis failed to reveal any deletion in the critical region for KS. Simultaneously, we report difficulties connected with the PCR technique based on the primers for KAL1 amplification presented in the literature. We designed primers that are specific to the X chromosome and bypass pseudogene KALY amplification.FISH analysis is a convenient screening technique, but in the presented family it failed to detect the deletion. Therefore, in the face of a distinctive manifestation of KS, a subsequent molecular assay should be introduced. The MLPA is a useful technique for differential diagnosis in patients with HH combined with smell impairment.

We report on a 3-year-old boy with moderate developmental retardation, microcephaly, and malformations of ears, lids, mouth, and thumbs. Cytogenetic analysis demonstrated a direct duplication of chromosome subregion 4(q21.3-->q31.3). Confirmation of this specific rearrangement was performed by fluorescent in situ hybridization (FISH) with a chromosome painting probe and by means of quantitative Southern hybridization with DNA probes localized within the chromosome 4 region presumed to be duplicated.

Myocardial infarction is followed by the inflammatory response of mezenchymal tissue leading to the debridement of the necrotic area as well as to initiation of repair followed by scar formation. The healing is a complex sequence of events consisted of four overlapping phases. Repair of the heart is under control of local and systemic regulatory factors. The knowledge of the mechanism of myocardial infarction allows to develop new strategies aimed at minimizing necrotic area and optimizing cardiac repair. This approach gives a chance to reduce the complications of myocardial infarction and to improve the quality of patients life.

The aim of the study was to analyze US/ECHO examinations in fetuses with diaphragmatic hernia (DH) diagnosed and treated in our institution from 1994-2006, and their follow-up.Retrospective analysis of the data base from Department for DiagnosesPrevention of Fetal Malformations, Research Institute of the Polish Mother's Memorial Hospital: 14,481 fetal echo/ultrasound examinations in 10,077 fetuses have been analyzed to retrieve 115 fetuses with DH.The mean gestational age at the targeted US/ECHO examination was 30 wks. There were 8 terminations of pregnancies (at mean 21 wks), 6 intrauterine demises, 60 neonatal deaths after delivery (in 1-3rd day of postnatal life), 8 deaths after surgery, 19 neonates were discharged home and in 14 cases the follow-up could not be monitored. The most common anomalies accompanying DH have been central nervous system anomalies (20%), polyhydramnion (16%) and cong heart defects (10%). In this subgroup, there was 100% mortality. Isolated DH has been diagnosed in every third case. In this subgroup, 27 neonates had undergone surgery and the survival rate was 70%, however since 2004 there was not a single death on record.Late gestational age of US/ECHO examinations in our tertiary center suggests that DH has been relatively difficult to detect during ultrasound screening. DH and the other structural malformations have been a lethal disease in our series in 100%. Isolated DH was much less frequent and was present in every third case (29%), and in this group the survival rate was 70%, regardless of the way of the delivery (CS or Vaginal).

To estimate the incidence of atherosclerosis risk factors in young men of Lodz city because of the highest in Poland fatality rate of circulatory system diseases.Anamnestic data on actual diseases, smoking, alcohol drinking and physical activity were achieved from 80 men, volunteers aged 20-39 years. Body weight and height, waist and hip circumference and arterial blood pressure were measured. Blood levels of lipids: total cholesterol (TCh), its fractions LDL, and HDL (LDL-Ch, HDL-Ch) ,and triglicerydes (TG), glucose, albumins, sex hormone binding globulin (SHBG), FSH, LH, total testosterone, dehydroepiandrosterone sulphate (DHEA-S) and estradiol were determined. Calculated were body mass index (BMI), waist to hip ratio (WHR), free testosterone index (FTI), free and bioactive testosterone.At least 3 atherosclerosis risk factors were simultaneously found in 33.7% of men, of which 22.7% were 20-29-year-old and 47.2% 30-39-year-old subjects. Elevated values of TG were found in 16.2% of men, TCh in 13.7%, LDL-Ch in 7.5% and decreased values of HDL-Ch in 6.2%. Positive significant correlations were found between WHR and TCh (R = 0.39; p = 0.01), LDL-Ch (R = 0.38; p = 0.02), TG (R = 0.41; p = 0.009). WHR negatively correlated with HDL-Ch (R = -0.31; p = 0.04). 50% of men had the excessive body weight. Obese men had abdominal type of obesity in 90%. As many as 62% of subjects had excessive systolic and 21% excessive diastolic arterial blood pressure. Blood pressure positively correlated with body weight (R = 0.51; p0.001), BMI (R = 0.51; p0.001), waist circumference (R = 0.55; p0.001) and WHR (R = 0.44; p0.001). In the whole group 35% of subjects led sitting life style and did not report any other physical activity. 57.5% of men were present or past smokers. 44% of men consumed alcohol everyday or almost everyday. FTI diminished with the advancing age, what was connected with the increase in SHBG blood concentration. There were no changes in total, free or bioactive testosterone, or LH and FSH concentrations with the age. Correlations between androgens and lipid profiles were not found. Estradiol blood levels negatively correlated with TG (R = -0.35; p = 0.03) and was significantly lower in 30-39-year-old men than in younger (20-29).The results indicate considerably higher incidence of atherosclerosis risk factors in young men, citizens of Lodz agglomeration, than it was found before for other regions of Poland. This phenomenon increases with the advancing age already between 20 and 39 years. Implementation of intensive prophylactic actions may prevent it.

The purpose of this cross-sectional study was to investigate whether environmental exposure to polycyclic aromatic hydrocarbons (PAHs) was associated with sperm aneuploidy. A sample of 181 men who attended an infertility clinic for diagnostic purposes and who had a normal semen concentration of 20–300 × 106 spermatozoa mL–1 or slight oligozoospermia (semen concentration of 15–20 × 106 spermatozoa mL–1; WHO 1999) provided urine and semen samples. Analysis of the level of PAH biomarker 1-hydroxypyrene (1-OHP) in urine was performed using high-performance liquid chromatography. Sperm aneuploidy was assessed using multicolour florescence in situ hybridisation (FISH) using DNA probes specific for chromosomes X, Y, 18, 13 and 21. Positive associations were observed between the level of 1-OHP in urine and total sex-chromosome disomy (P = 0.03) and chromosome-18 disomy (P = 0.03). These results suggest that environmental exposure to PAHs may be associated with sperm aneuploidy. This is the first epidemiological study to investigate the relationship between environmental exposure to PAHs and sperm aneuploidy. Therefore, these findings require further replication in other populations using different biomarkers of PAH exposure.

We report on a 6-year-old boy with moderate developmental retardation and unusual dermatoglyphics. Cytogenetic analysis demonstrated a duplication of chromosome sub-region 7p21.2-p14.2. Confirmation of the specific duplicated region was determined by quantitative Southern blotting by using a DNA fragment previously localized to the portion of chromosome 7 thought to be duplicated. This patient did not have the internal malformations seen with other dup(7p) patients.

This case report describes a 40-year-old woman, primigravida. On 13,3 weeks of gestation we diagnosed an abnormal flow pattern in the umbilical artery and abnormal hyperechogenic structure in fetal abdomen. In next sonographic examination on 16 weeks of gestation we diagnosed ventriculomegaly and ahydramnion. We also observed spina bifida, hyperechogenic kidneys, abnormal flow pattern in the umbilical vein and pulmonary valve insufficiency. We performed genetic amniocentesis. We observed complete trisomy in cytogenetic examinations. The woman opted for an elective TOP according to the Polish Abortion Act on 20 weeks of gestation.

To determine physiological variability range of the analyzed biometrical parameters and to establish optimal circumstances for fetal nasal ultrasound biometry. To evaluate preliminarily the value of fetal nasal biometry in the screening for aneuploidy.Ultrasound measurement of nasal bones length and nasal width in healthy fetuses and in fetuses with common aneuploidies.Measurements of the analyzed parameters were undertaken in 681 euploid fetuses and 9 fetuses with common aneuploidies. Nasal bones length was measured with accordance to the same set of rules as determined by Cicero et al. in their publication relating to the first trimester nasal bones assessment. Nasal width was measured in the coronal plane between the alae.Relationship between the examined parameters and gestational age was described. The normal variability range of the analyzed parameters was determined and percentile charts created. In three out of five examined fetuses with trisomy 21 the nasal bones length was below the 5th percentile. In one out of five trisomy 21 fetuses the nasal width was over the 95th percentile. Regrettably the paucity of data obtained from affected fetuses does not allow drawing statistically founded conclusions.Fetal nasal biometry seems to be a valuable screening marker of trisomy 21 in the second trimester, requiring further studies.

Polycystic ovary syndrome (PCOS) is a common heterogenous endocrine disorder associated with amenorrhoea (or oligomenorrhoea), hyperandrogenism, hirsutism, obesity, insulin resistance, and an approximately 7-fold increased risk of type 2 diabetes mellitus (NIDDM - non-insulin dependent diabetes mellitus). It is a leading cause of female infertility. The prevalence of PCOS among reproductive-age women has been estimated at 4%-12%. Familial aggregation of this syndrome is well established. There are also ethnic and racial variations in the prevalence of the syndrome and its symptoms. Multiple biochemical pathways have been implicated in the pathogenesis of PCOS. Several genes from these pathways have been tested include genes involved in steroid hormone biosynthesis and metabolism (StAR, CYP11, CYP17, CYP19 HSD17B1-3, HSD3B1-2), gonadotropin and gonadal hormones action (ACTR1, ACTR2A-B, FS, INHA, INHBA-B, INHC, SHBG, LHCGR, FSHR, MADH4, AR), obesity and energy regulation (MC4R, OB, OBR, POMC, UCP2-3), insulin secretion and action (IGF1, IGF1R, IGFBPI1-3, INS VNTR, IR, INSL, IRS1-2, PPARG) and many others. Most women with PCOS, both obese and lean, have a degree of insulin resistance. The minisatellite of insulin gene (INS VNTR), especially class III alleles and III/III genotypes might not only determine the predisposition to anovulatory PCOS but also the concomitant risk for development of type 2 diabetes. The function of the insulin receptor (IR) is probably normal in woman with PCOS. However abnormal serine phosphorylation in the receptor may impair signal transduction accounting for a post-binding defect in insulin action. Serine phosphorylation is also involved in the postranslational regulation of 17,20-lyase activity (CYP17). There may be a common aetiology for both insulin resistance and hyperandrogenism. Polymorphic alleles of both IRS-1 and IRS-2 (insulin receptor substrate 1 - 2), alone or in combination, may have a functional impact on the insulin-resistant component of PCOS. There is no evidence to suggest that follistatin gene polymorphisms play a role in the pathogenesis of insulin resistance in PCOS women. PCOS appears to be associated with the absence of the four-repeat-units allele in a polymorphic region of pentanucleotide (TTTTA)n repeats within CYP11A gene, which encodes cytochrome P450scc. It has been hypothesized that up-regulation of this enzyme could lead to increased androgen production. There is no evidence of any association of alleles of CYP19 gene (encoding cytochrome P450arom) with PCOS. Association exists between androgen receptor gene (AR) polymorphisms an androgens action in PCOS. Increased hirustism and decreased CAG repeat length within AR gene has been also demonstrated in women with normal testosterone levels. Expression of estrogen receptor (ERs) as well as 5-alpha-reeducates (SRD5A1-2 genes) activity was analysed in granulosa (GC) and theca cells (TC). The results of this study demonstrate that there are significant alterations in the expression of ERalpha and ERbeta in PCOS that may be related to abnormal follicular development. On the other hand elevated SRD5A activity in polycystic ovaries supported the hypothesis that 5-alpha-reduced androgens may play a role in the pathogenesis of the syndrome. The genetic aetiology of PCOS remains unknown. There are a number of interlinking factors that affects expression of PCOS. Single cause of PCOS is unlikely. Other possible mechanisms in pathogenesis of PCOS are discussed.

Rapid molecular biological methods for prenatal diagnosis of the most common aneuploidies, collectively known as rapid aneuploidy testing, are compared in this review. We discuss methodological problems and limitations of these various methods. All these techniques are believed to be accurate and carry a low risk of misdiagnosis, but they differ in terms of labour-intensity and amenability to automation and high throughput testing. The question how to apply them safely and economically in a clinical setting has not been answered yet. The discussed techniques are so far not used as stand-alone tests, but some of them are routinely applied as a preliminary test that shortens the waiting time for classic cytogenetic karyotyping. In the future, mainly because of economical reasons, these methods may replace cytogenetics in the category of patients who make up the majority of those currently offered prenatal karyotyping: patients with moderately increased risk and no abnormalities detected by ultrasound.

Two similar, but not identical, familial reciprocal translocations are described. In the first family, four sterile males inherited reciprocal translocation t(9;17)(q11'3) of maternal origin. In the second family, with the male fertility not impaired, reciprocal t(9;17)(q11;q11) was observed in four members of the family.

Editor—The SRY gene (sex determining region of Y) and AZF (azoospermia factor), a gene from a gene family with multiple members, are both localised on the Y chromosome and are crucial for testis determination and spermatogenesis, respectively.1-5 Sex reversal (XX males) may arise by translocation of sequences from Yp onto Xp owing to meiotic recombination. Eighty percent of XX males are SRY positive and in about one third of these the interchanges take place between the two PRK homologues, PRKX and PRKY , producing typical fusion fragments.6 Usually, genes from Yq including the AZF locus are not present in these cases and no spermatogenesis is found. We have decided to review, using molecular methods, a previously described7male true hermaphrodite with a left scrotal testis, oligozoospermia, and no detectable Y chromosome or its fragments on standard karyotype analysis. As described 24 years ago, the patient was referred to our laboratory because of short stature (1.5 m), right cryptorchidism, and gynaecomastia.7 At the time of explorative laparotomy, the ovary and female internal genitalia on the right side were removed. Biopsy of the left scrotal gonad showed Sertoli cells only. Clinically, true hermaphroditism was established. The patient was referred again when he was 44 years old. Because of increasing hardness and pain in the left epididymis and post inflammation changes observed by ultrasound, bacteriological analysis of semen was performed. Unexpectedly, spermatozoa were found. Their number ranged from a few to 500 000/ml in following tests. All spermatozoa were motionless; 70% of them were normal and 30% balloon headed. The semen samples were collected outside our clinic, so in order to confirm that they really were the patient's, the DNA profile was ascertained by VNTR (variable number of tandem repeats) testing with the probes MS1 (D1S7), MS31 (D7S21), …

The Cu-Zn superoxide dismutase (SOD1) activity was estimated in red blood cells in children with regular trisomy 21. We report patients displaying typical Down syndrome clinical features and with SOD1 activity in the normal range.

Two cases of a nonfluorescent Y (Ynf) chromosome were diagnosed: one in a male, the other in a female. Both bad similar complex mosaic chromosome constitutions with a 45,X cell line. DNA studies were applied in both cases for verification of the cytogenetic diagnosis. The results on the two patients were compared with data obtained from seven healthy men (46,XY), three healthy women (46,XX), two females with 46,XY karyotype, and from cell lines with 49,XXXXY and 48, XXXX chromosome constitution. The highly repetitive Y -specific DNA sequences located in the heterochromatic region of the long arm were absent in these patients. Differences in the composition of the euchromatic part of the Y chromosome were demonstrable in both patients. The highly repetitive Y -specific DNA sequences located in the heterochromatic region of the long arm were absent in these patients. Differences in the composition of the euchromatic part of the Y chromosome were demonstrable in both patients. The suggestion that the Ynf chromosome originates from a dicentric Y chromosome cannot be accepted as a complete explanation of the phenomenon, as it probably involves more complex molecular alterations of the abnormal Y chromosome. The presence of Ynf is associated with the presence of a 45,X cell line more often than in cases of simple Y chromosome deletions with the breakpoint localized in or below the Y euchromatin/heterochromatin junction.

A 3-year-old boy from twin pregnancy with the features of marked dystrophia from birth, deficient growth, considerable retardation of physical and mental development, numerous somatic defects, suspected congenital heart disease, and hypoplastic external genitalia, is reported. The 48,XXXX/49,XXXXY/49,XXXX,i(Yq) karyotype was diagnosed. The boy's brother, normally developed, had a 46,XY karyotype. It was found on the basis of serologic findings that the brothers were dizygotic twins.

Neural tube defects (NTD) are one of the more common congenital abnormalities with a generally accepted multifactorial origin, including a persistent environmental factor as well as a genetic factor, but with the precise cause still not known. Prenatal diagnosis of NTD uses a marker that is not a product of a defective gene or an abnormal chromosome, but is based upon the detection of elevated a,-fetoprotein (AFP) in the amniotic fluid [l]. The introduction of the qualitative amniotic fluid acetylcholinesterase test, in 1979, by Smith et al and Chubb et al [2,3] has gained wide acceptance as a secondary biochemical diagnostic test for the prenatal detection of NTD, thus improving the accuracy of the diagnosis. Qualitative description of the type of acetylcholinesterase in human amniotic fluid shows a typical form of this enzyme only in cases of open neural tube defects, but not in normal pregnancies [4-61. Gel electrophoresis separates non-specific cholinesterase from acetylcholinesterase on the basis of differential mobility: amniotic fluid from normal pregnancies has a single band which is a non-specific cholinesterase (ChE; EC 3.1.1.8), while NTD pregnancies have, additionally, a slightly faster-moving band which is acetylcholinesterase (AChE; EC 3.1.1.7) [7-121. AChE may be distinguished, additionally, from the non-specific ChE by the response to specific inhibitors [13]. AChE was originally chosen as a potential biochemical marker of NTD because of changes in its concentration associated with the development of the nervous