Translocation breakpoints of chromosome 4 in male carriers: clinical features and implications for genetic counseling.

Cytogenetic analysis remains a powerful and cost-effective technology, and has wide applicability in genetic counseling for infertile males. Chromosomal rearrangements are thought to be one of the major genetic factors that influence male infertility. Some carriers with balanced reciprocal translocation have been identified as having oligozoospermia or azoospermia, and there is an association between balanced translocation and recurrent abortion. Researchers have reported the involvement of chromosome 4 translocations in male factor infertility and recurrent miscarriages. A translocation breakpoint might interrupt the structure of an important gene, and it is associated with reproductive failure. However, the clinical characteristics of the breakpoints in chromosome 4 translocations have not been studied. Here, we report the breakpoints in chromosome 4 translocation and the clinical features presented in carriers to enable informed genetic counseling of these patients. Of 82 patients with balanced reciprocal translocations, 14 were carriers of the chromosome 4 translocation: four presented with pregestational infertility (clinical manifestations: oligozoospermia, severe oligozoospermia, or azoospermia), whereas 10 presented with gestational infertility (able to conceive but with a tendency to miscarry). The breakpoint at 4q12 was associated with pregestational infertility, whereas the breakpoints at 4q13, 4q21, 4q25, and 4q32 were associated with gestational infertility. However, the breakpoint at 4q35 was associated with both pregestational and gestational infertility. Chromosome 4 translocation carriers with pregestational or gestational infertility should be counseled on chromosomal breakpoints and the different technologies available to assist reproduction.

Translocation breakpoints of chromosome 1 in male carriers: clinical features and implications for genetic counseling.

Reciprocal translocation is closely associated with male infertility and recurrent miscarriages. Balanced reciprocal translocations associated with reproductive failures are predominantly observed on chromosome 1. Additionally, infertile male patients present a number of breakpoints throughout chromosome 1. A translocation breakpoint might interrupt the structure of an important gene, leading to male infertility. Here, we report the breakpoints on chromosome 1 translocation and the clinical features presented in carriers, to enable informed genetic counseling of these patients. Balanced reciprocal translocations were found in 1.57% of the tested patients. Among 82 patients, 23 patients (28.05%) were carriers of the chromosome 1 translocation: 12 presented pre-gestational infertility with clinical manifestations of azoospermia or oligozoospermia, while 11 patients presented gestational infertility (able to conceive but with a tendency to miscarry or give birth to a stillborn). The breakpoint at 1p22 was predominantly observed in these patients; additionally, breakpoints at 1p31.2, 1p10, and 1q25 were associated with gestational infertility. Breakpoints at 1p13, 1q12, and 1q21 were associated with pre-gestational infertility. These results suggested that breakpoints at 1p32, 1p13, and 1q21 were predominantly associated with pre-gestational infertility, while that at 1q25 was associated with gestational infertility. Chromosome 1 translocation carriers with infertility presenting as azoospermia or oligospermia should be counseled on chromosomal breakpoints and the different molecular technologies available to facilitate reproduction.

Chromosome 7 translocation breakpoints in male carriers: clinical features and implications for genetic counseling.

Balanced reciprocal translocations are associated with reproductive failure. Some reciprocal translocation carriers exhibit azoospermia or oligozoospermia, and an association exists between these chromosomal abnormalities and recurrent abortion. Previous reports have indicated the involvement of chromosome 7 translocations in male infertility and recurrent miscarriage. A translocation breakpoint can occur within an important gene, interrupting its structure and leading to male infertility. However, clinical characteristics resulting from chromosome 7 translocation breakpoints have not been studied. Here, we report such breakpoints and their associated clinical features, to enable informed genetic counseling of carriers. Balanced reciprocal translocations were found in 1.57% of the tested patients. Among these 82 individuals, 14 (17.07%) carried a chromosome 7 translocation, of which, five presented with pregestational infertility and clinical manifestations of oligozoospermia or necrospermia, while nine presented with gestational infertility (i.e., were able to conceive, but often resulting in miscarriage). Breakpoints at 7q31 and 7q36 were associated with pregestational infertility, whereas those at 7p10, 7q21.2, 7q22, and 7q32 were connected to gestational infertility. However, the breakpoint at 7p15 was associated with both. Chromosome 7 translocation carriers with pregestational or gestational infertility should be counseled on chromosomal breakpoints and the various molecular technologies available for assisted reproduction.

Balanced reciprocal translocation at amniocentesis: cytogenetic detection and implications for genetic counseling.

Balanced translocation is a common structural chromosomal rearrangement in humans. Carriers can be phenotypically normal but have an increased risk of pregnancy loss, fetal death, and the transmission of chromosomal abnormalities to their offspring. Existing prenatal screening technologies and diagnostic procedures fail to detect balanced translocation, so genetic counseling for carriers remains a challenge. Here, we report the characteristics of chromosomal reciprocal translocation in 3807 amniocentesis cases. Of the 16 detected cases of fetal reciprocal translocation, 8 cases (50%) showed positive biochemical marker screening; 3 cases (18.75%) were the parental carriers of a chromosomal abnormality; 2 (12.5%) were of advanced maternal age, 2 (12.5%) had a previous history of children with genetic disorders, and 1 case (6.25%) was associated with positive soft markers in obstetric ultrasound. Chromosomes 5 and 19 were the most commonly involved chromosomes in balanced translocations. Of the 13 cases with fetal balanced translocations, 8 (61.5%) were inherited from a paternal chromosome, 3 (23.1%) from a maternal chromosome, and 2 (15.4%) cases were de novo. The incidence of balanced translocation at amniocentesis was 0.42%. Male carriers of reciprocal chromosome translocation appear to have a higher chance of becoming a parent of a child born by normal childbirth than female carriers.

Correlation of VCAM-1 expression in serum, cord blood, and placental tissue with gestational hypertension associated with fetal growth restriction in women from Xingtai Hebei, China.

The aim of this study was to investigate the expression of vascular adhesion molecule (VCAM)-1 in the maternal serum, cord blood, and placental tissue of pregnant women from Xingtai, Hebei, with gestational hypertension (GH) combined with fetal growth restriction (FGR). A total of 108 patients with GH combined with FGR (GH-FGR), 60 patients with GH alone (GH), and 50 healthy pregnant women (control) were recruited to this study. VCAM- 1 expression was detected in the maternal serum and cord blood by enzyme-linked immunosorbent assay, and in the placental tissue by immunohistochemistry. VCAM-1 expression was significantly higher in the maternal serum of patients with GH-FGR (164.38 ± 60.35) and GH alone (103.85 ± 54.47) than in the serum of the control population (46.70 ± 21.79; P < 0.05). On the other hand, VCAM-1 expression in the cord blood of GH-FGR (163.19 ± 69.46), GH (149.82 ± 58.20), and control (128.89 ± 43.59) subjects was not significantly different (P > 0.05). Moreover, the VCAM-1 expression rates were significantly higher and lower in the vascular endothelial and trophoblastic cells of the placenta of patients with GH-FGR (74.71 and 56.1%) and GH (72.98 and 55.36%), respectively, compared to those in the control subjects (46.48 and 95.11%). Therefore, we concluded that VCAM- 1 plays an important role in the development and generation of GH. Additionally, the low VCAM-1 expression in the trophoblastic cell could be correlated to the pathogenesis and progression of GH.

Role of ABCB1 C1236T, G2677T, and C3435T genetic polymorphisms in the development of acute leukemia in a Chinese population.

We carried out a case-control study to examine the relationship between the ATP-binding cassette subfamily B member 1 (ABCB1) gene polymorphisms C1236T, G2677T, and C3435T and risk of acute leukemia in a Chinese population. Between May 2013 and April 2015, we recruited 164 acute leukemia patients and 285 healthy controls, and determined polymorphism genotypes by polymerase chain reaction-restriction fragment length polymorphism. Using unconditional logistic regression analysis, we observed that in comparison to the wild-type sequence, the TT genotype [odds ratio (OR) = 2.15, 95% confidence interval (CI) = 1.12-4.10; P = 0.01] and the T allele (OR = 1.39, 95%CI = 1.05-1.86; P = 0.02) of ABCB1 G2677T were associated with acute leukemia susceptibility. The TT genotype (OR = 2.03, 95%CI = 1.11- 3.69; P = 0.01) and the T allele (OR = 1.39, 95%CI = 1.05-1.85; P = 0.02) of the C3435T polymorphism also increased acute leukemia risk compared to the wild-type form. However, no significant relationship was established between the ABCB1 C1236T variant and this disease. Our results suggest that the ABCB1 G2677T and C3435T sequence variations may affect susceptibility to acute leukemia.

De novo interstitial deletion in the long arm of chromosome 11: a case report.

The 11q terminal deletion disorder is a rare genetic disorder associated with numerous clinical features. A few case reports have been made about de novo interstitial deletion of chromosome 11q. However, due to the heterogeneity in size and position of the deletions, a clear genotype-phenotype correlation is not easily made. Here we report a case interstitial 20.5-Mb deletion at chromosome 11q13.4q21, as confirmed by array comparative genomic hybridization. Dysmorphic features such as coarse facial features, congenital laryngomalacia, oblique inguinal hernia, high-arched palate, and camptodactyly were observed in the subject. The present case broadens the spectrum of clinical findings observed in individuals with 11q interstitial deletion.

Overexpression of forkhead box protein M1 (FOXM1) plays a critical role in colorectal cancer.

BACKGROUND: The forkhead box M1 (FOXM1), an important regulator of cell differentiation and proliferation, is overexpressed in a number of aggressive human carcinomas. However, the clinical significance of FOXM1 signaling in human colorectal cancer (CRC) pathogenesis remains unknown. The aim of this study was to evaluate the role of FOXM1 in CRC tumorigenesis. METHODS: We investigated FOXM1 expression in 103 cases of primary CRC and matched normal tissue specimens and explored the underlying mechanisms of altered FOXM1 expression and the impact of this altered expression on CRC proliferation and metastasis using in vitro models of CRC. RESULTS: The results showed that high expression of FOXM1 staining was 85.44% (88/103) in 103 cases of CRC and 20.39% (21/103) in 103 cases of adjacent non-cancerous tissue samples; the difference of FOXM1 expression between two groups was statistically significant (P < 0.001). Silencing of FOXM1 inhibited the proliferation of CRC cells, and the invasion and migration of CRC cells were distinctly suppressed. Furthermore, FOXM1 knockdown led to substantial reductions in VEGF-A levels in CRC cell lines. CONCLUSIONS: Our data suggest that the pathogenesis of CRC maybe mediated by FOXM1, and FOXM1 could represent selective targets for the molecularly targeted treatments of CRC.

Physiological evaluation of the responses of Larix olgensis families to drought stress and proteomic analysis of the superior family.

The conifer Larix olgensis has been analyzed to delineate physiological and proteomic changes that occur under drought stress. Studies of the deleterious effects of drought in the larch families have mainly focused on photosynthesis. In the present study, when the intensity of drought was increased, plant height was inhibited as both POD and MDA levels increased, which indicates oxidative stress. Two-dimensional gel electrophoresis analysis detected 23 significantly differentially expressed proteins, of which 18 were analyzed by peptide mass fingerprinting by using MALDI-TOF/TOF. Eight spots were found to be up-regulated, while the other 10 spots were down-regulated during drought stress. The proteins that were induced by drought treatment have been implicated in the physiological changes that occurred. These results could provide additional information that could lead to a better understanding of the molecular basis of drought-sensitivity in larch plants.

Reproductive outcome of a case with familial balanced translocation t(3;6): implications for genetic counseling.

Although it is known that parental carriers of structural chromosomal rearrangements are associated with recurrent pregnancy loss, subsequent natural pregnancies remain possible. We examined the reproductive outcome of a familial balanced translocation with t(3;6)(q12;q27). Karyotyping of the proband revealed 46,XY chromosomes with the balanced translocation t(3;6). The first 2 pregnancies resulted in spontaneous abortions. Based on the proband karyotype, his father and half-brother were subjected to cytogenetic analysis, and both showed 46,XY, t(3;6)(q12;q27). After genetic counseling, the proband chose to continue the pregnancy. During the third pregnancy, the subject gave birth to a normal male infant. For parental carriers with balanced chromosomal translocations, natural pregnancy should be considered during genetic counseling.

Male carriers of balanced reciprocal translocations in Northeast China: sperm count, reproductive performance, and genetic counseling.

Balanced chromosomal translocations in men can cause failure of spermatogenesis owing to meiotic impairment. Male carriers may exhibit normozoospermia, although clinical manifestations can include oligozoospermia or azoospermia, oligozoospermia or normozoospermia. Here, we reported the characteristics of balanced reciprocal translocations in men from northeastern China, and explored the relationship between sperm count and reproductive performance, to enable informed genetic counseling. The frequency of balanced reciprocal translocations was found to be 1.62%. Semen analysis showed that 5.9% of male carriers had azoospermia, 43.1% had oligozoospermia, and 51.0% had normozoospermia. Of the 25 men with a balanced reciprocal translocation and azoospermia or oligozoospermia, chromosome 1 was the most commonly often involved in the translocation. However, in the 26 normozoospermic men with a balanced reciprocal translocation and normozoospermia, chromosome 3 was most commonly implicated. Fifty percent of men with a balanced reciprocal translocation conceived a pregnancy that went to term. Our data suggest that of all chromosomes, chromosomes 1 and 3 are the most commonly involved chromosomes in balanced reciprocal such translocations in northeastern Chinese men. Karyotype analysis should be performed for men with azoospermia, oligozoospermia, and those in couples having suffered recurrent miscarriages. Natural conception should be discussed during genetic counseling for male carriers of balanced chromosomal translocations with normozoospermia.

An outbreak of Candida parapsilosis fungemia among preterm infants.

In this article, we describe the first outbreak of Candida parapsilosis fungemia in our hospital. We examined a cluster of four nosocomial cases of C. parapsilosis fungemia that occurred in the neonatal intensive care unit (NICU) of the Affiliated Xingtai People's Hospital of Hebei Medical University over a two-week period. We ascertained patient parameters including clinical characteristics, blood and sputum cultures, and drug sensitivity test results. Cultures from eight blood samples obtained from the four infected preterm infants showed identical characteristics and were identified as C. parapsilosis. In order to determine the infection-related factors and to control the spread of the infection among the population, we immediately initiated the emergency plan. All four of the preterm infants recovered from the infection; there were no deaths. Outbreaks of C. parapsilosis, mostly involving preterm infants of very low birth weight or extremely low birth weight, can and do occur in NICUs. Cultures prepared using multiple samples taken from different patients contribute to a more definitive diagnosis. Established measures that control and prevent the infection, as well as effective and comprehensive treatments, can lead to a favorable outcome. That is to say, improving both disinfection and isolation, as well as interrupting the pathway of transmission, is the key to controlling the spread of infection.

Sperm retrieval from patients with nonmosaic Klinefelter's syndrome by semen cytology examination.

Successful sperm retrieval from ejaculates of nonmosaic Klinefelter's syndrome (KS) patients by using semen cytology examination was described in this report. The clinical parameters of KS patients with sperm compared to patients without sperm were described. One hundred and fifty-one patients were proven to suffer from KS by chromosomal analysis using G-banding. Spermatozoa were obtained from 10 patients (10/151, 6.6%) using semen analysis. After semen cytology examination, 32 patients (32/151, 21.2%) were found to have sperm or germ cell in their ejaculate. The patients with successful sperm retrieval were significantly younger (27.1 ± 3.7 years) than the patients for whom sperm retrieval failed (28.9 ± 4.2 years). The mean serum testosterone level and the mean T/LH ratio of KS patients with successful sperm retrieval were significantly higher in men with sperm than in men without sperm (testosterone: 3.2 ± 2.1 ng/mL vs 2.7 ± 1.5 ng/mL; T/LH ratio: 0.2 ± 0.3 vs 0.1 ± 0.1). In conclusion, semen cytology examination should be performed to identify sperm and germ cells in the ejaculate of KS patients if no sperm can be detected by traditional semen analysis. The serum testosterone level and T/LH ratio revealed an association between impaired Leydig cell function and impaired spermatogenesis in KS males. KS patients should receive earlier diagnosis and treatment.

Male infertility in Northeast China: molecular detection of Y chromosome microdeletions in azoospermic patients with Klinefelter's syndrome.

The prevalence of microdeletions of azoospermia factor (AZF) among azoospermic Klinefelter's syndrome (KFS) patients shows conflicting data. We aimed to detect this frequency in a Northeast Chinese population, and to investigate the possible association between AZF microdeletions and KFS by comparison with previous conflicting reports. Eighty men affected with KFS and a random healthy control group comprising 60 fertile men and women were recruited. AZF microdeletions were detected by multiplex polymerase chain reaction using 9 specific sequence-tagged sites. Karyotype analyses were performed on peripheral blood lymphocytes using standard G-banding. Finally, azoospermia was confirmed in 77 men affected with KFS and no AZF microdeletions were found. Karyotype analysis revealed 1 patient with karyotype 47,XXY,inv (9) (p11, q13), and 2 with mosaic karyotypes (46,XX/47,XXY and 46,XY/47,XXY). All other patients had karyotype 47,XXY. Review of the literature showed that these results were similar to those of other regions of Northeast Asia, but differed from those obtained from Caucasian populations. Our results supported the proposal that AZF microdeletions and KFS result from separate genetic defects. The prevalence of AZF in azoospermic KFS patients varies among populations, and it might result from genetic drift or selective pressure. These results suggest that routine screening for classical AZF microdeletions among infertile azoospermic men with a 47,XXY karyotype might not be necessary in Northeast Chinese individuals. However, it remains imperative for patients considering assisted reproductive treatments, particularly for those with mosaic karyotypes.

Analysis of genetic diversity in Larix gmelinii (Pinaceae) with RAPD and ISSR markers.

Dahurian larch (Larix gmelinii), a deciduous conifer, is the northernmost tree, native to eastern Siberia and nearby regions of China. We used growth traits and molecular markers to assess genetic variation in different L. gmelinii growing regions; 105 individual samples were collected from seven regions of the Qingshan Forestry Centre, Heilongjiang Province, China. The greatest genetic regional variation was seen in the Youhao area, based on coefficients of variation for tree height, diameter and volume (14.73, 28.25, and 55.27%, respectively). Analysis using molecular markers showed rich genetic diversity. The RAPD and ISSR methods both indicated that most variation came from within populations. The seven regions were divided into two groups (Daxing'an and Xiaoxing'an Mountain ranges) by RAPD cluster analysis: Tianchi, Xiaojiuya, Yuanjiang, and Taiping regions were placed in the first group at a genetic distance of 0.08; while the other regions were in the second group. The correlation between RAPD markers and geographical distance was significant, with a correlation coefficient of 0.752.