Molecular cytogenetic characterization of de novo concomitant distal 8p deletion of 8p23.3p23.1 and Xp and Xq deletion of Xp22.13q28 due to an unbalanced X;8 translocation detected by amniocentesis.

OBJECTIVE: We present molecular cytogenetic characterization of de novo concomitant distal 8p deletion of 8p23.3p23.1 and Xp and Xq deletion of Xp22.13q28 due to an unbalanced X;8 translocation detected by amniocentesis. CASE REPORT: A 33-year-old primigravid woman underwent amniocentesis at 18 weeks of gestation because of a Down syndrome risk of 1/52 at the first-trimester maternal serum screening calculated from 0.29 multiples of the median (MoM) of pregnancy associated plasma protein-A (PAPP-A), 1.14 MoM of free ß-hCG and 0.46 MoM of placental growth factor (PlGF). Amniocentesis revealed a karyotype of 45,X,add(8)(p23.1). The parental karyotypes were normal. Array comparative genomic hybridization (aCGH) analysis on the DNA extracted from cultured amniocytes revealed a 137-Mb deletion of Xp22.13q28 and a 10.53-Mb deletion of 8p23.3p23.1. The karyotype thus was 45,X,der(8)t(X;8)(p22.13;p23.1). Prenatal ultrasound revealed pericardial effusion and skin edema. The pregnancy was subsequently terminated, and a 568-g malformed fetus was delivered with hypertelorism and low-set ears. The cord blood had a karyotype of 45,X,der(8)t(X;8)(p22.13;p23.1). aCGH analysis of the cord blood revealed the result of arr [GRCH37 (hg19)] 8p23.3p23.1 (191,530-10,724,642) × 1.0, arr Xp22.13q28 (18,194,098-155,232,907) × 1.0. CONCLUSION: aCGH analysis is useful elucidating the genetic nature of an aberrant chromosome with an additional maternal of unknown origin attached to a chromosome terminal region.

A novel reference chart and growth standard of fetal biometry in the Taiwanese population.

OBJECTIVE: The purpose of this study was to establish a new reference chart and growth standards for fetal biometry in Taiwan. MATERIALS AND METHODS: 2047 singleton pregnancies were enrolled in this study with 15,813 fetal scans between 18 and 40 gestational weeks. A reference chart and normal range for fetal biparietal diameter (BPD), abdominal circumference (AC) and femur length (FL) was established by longitudinal quantile regression model. 330 women with comorbidities including gestational hypertension, preeclampsia and gestational diabetes were excluded and 1717 pregnant women were enrolled for the growth standard. RESULTS: The new reference values were significantly larger across all gestational ages compared with the prior National Taiwan University reference chart in 1983. Compared with Intergrowth-21st, the BPD was larger at 18-23 weeks, the AC was larger at 18-24 weeks and the FL was larger at 18-36 weeks whereas they were all smaller at 29-40 weeks for the BPD, at 32-40 weeks for the AC and at 38-40 weeks for the FL. A quantile regression equation of biometry was established. BPD, AC, and FL had weekly growth of 2.5, 9.87 and 2.15 mm. Prepregnancy body weight, height, age, and gestational diabetes increased fetal size. Both gestational and chronic hypertension decreased fetal size. CONCLUSION: To promote maternal-fetal safety, a new reference chart and growth standard for fetal biometry is necessary to measure fetal growth.

iDPGK: characterization and identification of lysine phosphoglycerylation sites based on sequence-based features.

BACKGROUND: Protein phosphoglycerylation, the addition of a 1,3-bisphosphoglyceric acid (1,3-BPG) to a lysine residue of a protein and thus to form a 3-phosphoglyceryl-lysine, is a reversible and non-enzymatic post-translational modification (PTM) and plays a regulatory role in glucose metabolism and glycolytic process. As the number of experimentally verified phosphoglycerylated sites has increased significantly, statistical or machine learning methods are imperative for investigating the characteristics of phosphoglycerylation sites. Currently, research into phosphoglycerylation is very limited, and only a few resources are available for the computational identification of phosphoglycerylation sites. RESULT: We present a bioinformatics investigation of phosphoglycerylation sites based on sequence-based features. The TwoSampleLogo analysis reveals that the regions surrounding the phosphoglycerylation sites contain a high relatively of positively charged amino acids, especially in the upstream flanking region. Additionally, the non-polar and aliphatic amino acids are more abundant surrounding phosphoglycerylated lysine following the results of PTM-Logo, which may play a functional role in discriminating between phosphoglycerylation and non-phosphoglycerylation sites. Many types of features were adopted to build the prediction model on the training dataset, including amino acid composition, amino acid pair composition, positional weighted matrix and position-specific scoring matrix. Further, to improve the predictive power, numerous top features ranked by F-score were considered as the final combination for classification, and thus the predictive models were trained using DT, RF and SVM classifiers. Evaluation by five-fold cross-validation showed that the selected features was most effective in discriminating between phosphoglycerylated and non-phosphoglycerylated sites. CONCLUSION: The SVM model trained with the selected sequence-based features performed well, with a sensitivity of 77.5%, a specificity of 73.6%, an accuracy of 74.9%, and a Matthews Correlation Coefficient value of 0.49. Furthermore, the model also consistently provides the effective performance in independent testing set, yielding sensitivity of 75.7% and specificity of 64.9%. Finally, the model has been implemented as a web-based system, namely iDPGK, which is now freely available at http://mer.hc.mmh.org.tw/iDPGK/ .

Prenatal diagnosis of mosaicism for trisomy 7 in a single colony at amniocentesis in a pregnancy with a favorable outcome.

OBJECTIVE: We present prenatal diagnosis of mosaicism for trisomy 7 in a single colony at amniocentesis with a favorable outcome. CASE REPORT: A 40-year-old woman underwent amniocentesis at 17 weeks of gestation because of advanced maternal age. Amniocentesis revealed a result of 47,XY,+7[1]/46,XY[26]. In 27 colonies of cultured amniocytes, all five cells in one colony had trisomy 7, while the rest 26 colonies had a normal karyotype. The parental karyotypes were normal. Repeat amniocentesis was performed at 19 weeks of gestation. Interphase fluorescence in situ hybridization (FISH) was applied on the uncultured amniocytes, and the result showed trisomy 7 signals in 4% (3/75 cells) of the uncultured amniocytes compared with 1.4% (1/70 cells) in the normal control. Uniparental disomy (UPD) 7 was excluded by polymorphic DNA marker analysis. The cultured amniocytes at repeat amniocentesis had a karyotype of 46,XY. Prenatal ultrasound findings were unremarkable. A healthy 3332-g male baby was delivered at 38 weeks of gestation. The karyotype of cord blood lymphocytes was 46,XY. The boy was phenotypically normal at age 8 months at follow-up. No trisomy 7 signal could be detected in the postnatal FISH analysis of the urinary cells. CONCLUSION: Mosaicism for trisomy 7 in a single colony at amniocentesis without UPD 7 can be associated with a favorable outcome.

Genome-wide discovery of viral microRNAs based on phylogenetic analysis and structural evolution of various human papillomavirus subtypes.

In mammals, microRNAs (miRNAs) play key roles in controlling posttranscriptional regulation through binding to the mRNAs of target genes. Recently, it was discovered that viral miRNAs may be involved in human cancers and diseases. It is likely that viral miRNAs help viruses enter the latent phase of their life cycle and become undetected by the host's immune system, while increasing the host's risk for cancer development. Cervical cancer is typically related to the infection of human papillomavirus (HPV) through sexual transmission. To further understand the molecular mechanisms underlying the associations of HPV infection with genital diseases, we developed a systematic method for viral miRNA identification and viral miRNA-mediated regulatory network construction based on genome-wide sequence analysis. The complete genomes of certain high-risk HPV subtypes were used to predict putative viral pre-miRNAs by bioinformatics approaches. In addition, small RNA libraries in human cervical lesions from existing publications were collected to validate the predicted HPV pre-miRNAs. For the construction of virally encoded miRNA-mediated regulatory network of HPV infection, cervical squamous epithelial carcinoma gene expression data were extracted from the RNA sequencing platform in The Cancer Genome Atlas; the differentially expressed genes were used to identify the putative targets of viral miRNAs. Predicted cellular target genes of HPV-encoded miRNAs provide an overview of these viral miRNA's putative functions. Finally, a large-scale genome analysis was carried out to examine the phylogenetic relationship and structural evolution among genital HPV types that have the potential to cause genital cancer. In this study, we discovered putative HPV-encoded miRNAs, which were validated against the small RNA libraries in human cervical lesions. Furthermore, as indicated by their biological functions, host genes targeted by HPV-encoded miRNAs may play significant roles in virus infection and carcinogenesis. These viral miRNAs pose as promising candidates for the development of antiviral drugs. More importantly, the identified subtype-specific miRNAs have the potential to be used as biomarkers for HPV subtype determination.

Prenatal diagnosis of an 8q22.2-q23.3 deletion associated with bilateral cleft lip and palate and intrauterine growth restriction on fetal ultrasound.

OBJECTIVE: We present prenatal diagnosis of an interstitial 8q22.2-q23.3 deletion associated with bilateral cleft lip and palate and intrauterine growth restriction (IUGR) on fetal ultrasound. CASE REPORT: A 29-year-old, primigravid woman underwent elective amniocentesis at 17 weeks of gestation because of anxiety. Amniocentesis revealed a karyotype of 46, XX. However, level II ultrasound at 21 weeks of gestation revealed a fetus with IUGR and bilateral cleft lip and palate. Repeat amniocentesis was performed at 21 weeks of gestation, and array comparative genomic hybridization using uncultured amniocytes revealed a 13.5-Mb interstitial deletion of 8q22.2-q23.3 encompassing 37 Online Mendelian Inheritance of in Man (OMIM) genes including SPAG1, GRHL2, NCALD, RRM2B and ZFPM2. Polymorphic DNA marker analysis determined a paternal origin of the deletion. The pregnancy was subsequently terminated, and a malformed fetus was delivered with a depressed nose and bilateral cleft lip and palate. CONCLUSION: Prenatal diagnosis of facial cleft with IUGR should raise a suspicion of subtle chromosome deletions.

Prenatal diagnosis and molecular cytogenetic characterization of mosaicism for a small supernumerary marker chromosome derived from chromosome 2.

OBJECTIVE: We present prenatal diagnosis and molecular cytogenetic characterization of mosaicism for a small supernumerary marker chromosome (sSMC) derived from chromosome 2. CASE REPORT: A 42-year-old woman underwent amniocentesis at 17 weeks of gestation because of advanced maternal age. Amniocentesis revealed a karyotype of 47,XY,+mar[10]/46,XY[12]. The parental karyotypes were normal. Array comparative genomic hybridization analysis of the DNA extracted from cultured amniocytes revealed no genomic imbalance. Spectral karyotyping analysis failed to identify the sSMC. Metaphase fluorescence in situ hybridization analysis using the satellite probes CEP1/5/19, CEP2, CEP3, CEP4, CEP6, CEP7, CEP8, CEP9, CEP10, CEP12, CEP13/21, CEP14/22, CEP15, CEP16, and CEP20 revealed a result of 47,XY,+mar .ish der(2)(D2Z+)[10]. The sSMC was derived from the α satellite of chromosome 2. Polymorphic DNA marker analysis using the markers specific for chromosome 2 on the DNAs extracted from cultured amniocytes and parental bloods excluded uniparental disomy 2. At 39 weeks of gestation, a healthy 3394-g male baby was delivered with no phenotypic abnormality. The cord blood had a karyotype of 47,XY,+mar[21]/46,XY[19]. CONCLUSION: Array comparative genomic hybridization and spectral karyotyping may fail to detect an sSMC derived from α satellite, which needs satellite probes for confirmation.

Preoperative measurement of maternal abdominal circumference relates the initial sensory block level of spinal anesthesia for cesarean section: An observational study.

OBJECTIVE: Lumbosacral cerebrospinal fluid volume is decreased as the enlarging uterus compresses the inferior vena cava during pregnancy. A subsequent greater cephalad spread of sensory blockade is observed. Gravid uterus plays a crucial role in affecting the spinal anesthesia level. We hypothesized that maternal abdominal circumference can reflect compressive effect of the uterus and investigated the relationship between abdominal circumference and the level of sensory blockade, and incidence of hypotension following spinal anesthesia with hyperbaric bupivacaine in term parturients. MATERIALS AND METHODS: Forty-two term parturients scheduled for elective cesarean section were studied. Abdominal circumference was measured before spinal anesthesia; 0.5% hyperbaric bupivacaine (2 mL, 2.2 mL, or 2.4 mL) was injected in to the subarachnoid space at the L3-L4 intervertebral level according to the parturient's height. The level of sensory blockade was assessed using an ice cube 1 minute, 5 minutes, 10 minutes, and 15 minutes after the spinal injection. The level of sensory blockade at the 15th minute was defined as the level of maximum sensory blockade. Statistical correlation coefficients were evaluated with Spearman's rank correlation. RESULTS: The correlation coefficient between the abdominal circumference and spinal level measured by cold sensation loss at 5 minutes after spinal anesthesia was significantly positive (right side ρ=0.43, p=0.005; left side ρ=0.46, p=0.003). No significant correlation was found between abdominal circumference and the level of maximum sensory blockade, the incidence of hypotension, ephedrine dosage, nausea, and vomiting after spinal anesthesia. CONCLUSION: Parturients with greater abdominal circumference value have a higher level of sensory blockade at 5 minutes after spinal anesthesia. Abdominal circumference cannot predict the maximum sensory blockade level and the incidence of hypotension.

Rapid aneuploidy diagnosis by multiplex ligation-dependent probe amplification and array comparative genomic hybridization in pregnancy with major congenital malformations.

OBJECTIVE: To report five cases of major congenital malformations associated with common aneuploidies detected by rapid aneuploidy diagnosis. CASE REPORTS: The fetus in the first case presented cebocephaly, semilobar holoprosencephaly, and tetralogy of Fallot on ultrasound at 25 gestational weeks. Cordocentesis using multiplex ligation-dependent probe amplification to detect aneuploidies of chromosomes X, Y, 13, 18, and 21 in uncultured cord blood revealed three copies of all targets on chromosome 13 consistent with the diagnosis of trisomy 13. The fetus in the second case presented bilateral choroid plexus cysts, congenital diaphragmatic hernia, and club foot on ultrasound at 18 gestational weeks. Amniocentesis using array-based comparative genomic hybridization (aCGH) in uncultured amniocytes revealed a gain in the DNA dosage of chromosome 18 consistent with the diagnosis of trisomy 18. The fetus in the third case presented aortic stenosis and nuchal edema on ultrasound at 22 gestational weeks. Amniocentesis using aCGH in uncultured amniocytes revealed a result of monosomy X and Turner syndrome. The fetus in the fourth case presented nuchal cystic hygroma and ventriculomegaly on ultrasound at 17 gestational weeks. Amniocentesis using aCGH in uncultured amniocytes revealed a gain in the DNA dosage of chromosome 21 consistent with the diagnosis of trisomy 21. The fetus in the fifth case presented holoprosencephaly, omphalocele, and hydronephrosis on ultrasound at 17 gestational weeks. Amniocentesis using aCGH in uncultured amniocytes revealed a gain in the DNA dosage of chromosome 13 consistent with the diagnosis of trisomy 13. CONCLUSIONS: Prenatal diagnosis of major congenital malformations should alert one to the possibility of chromosomal abnormalities. Multiplex ligation-dependent probe amplification and aCGH have the advantage of rapid aneuploidy diagnosis of common aneuploidies in cases with major congenital malformations.

Mercury concentration in meconium and risk assessment of fish consumption among pregnant women in Taiwan.

Meconium is a matrix that can be obtained easily and noninvasively and is useful for detecting antenatal fetal exposure to environmental toxins. Taiwan is an island with high fish consumption, and many pregnant women would like to enjoy the benefits of fish without jeopardizing their health or that of their child. The aim of this study is to assess the mercury concentration in meconium in relation to the health risk of mercury exposure. A total of 198 mother-infant pairs residing in the city of HsinChu were recruited for the study between January 2007 and June 2007. The average mean concentration of mercury in meconium was 79.2+/-7.3 ng g(-1) dry wt We use the Monte Carlo technique to assess the uncertainty in risk assessment and the impact of these uncertainties on the estimation of expected risk of mercury intake from fish in mothers. Based on the FAO/WHO's tolerable daily intake of methylmercury (0.23 microg kg(-1)d(-1)), we found that 17.3% and 14.0% of the daily mercury exposure estimated exceeded the reference dose for foreign-born and Taiwan-born mothers, respectively. We found that the mercury concentration in meconium was much higher than in other studies, except for one study done in Tagum in the Philippines where mercury is used in gold mining. This may be because Asia is the largest emitter of anthropogenic mercury, accounting for 53% of worldwide emissions. Sensitivity analysis suggests that mercury concentration in fish and the rate of ingesting fish may be the key parameters for governments offering risk management guidance to protect the health of mothers and unborn babies.

Huge pelvic mass, cutaneous and vaginal fistulas, and bilateral hydronephrosis: a rare presentation of actinomycosis with a good response to conservative treatment and with long-term sequelae of renal atrophy and hydronephrosis.

OBJECTIVE: Actinomycosis with an extended pelvic abscess is an uncommon condition, which usually occurs coincident with the presence of an intrauterine contraceptive device (IUD) in the uterine cavity. The clinical picture of pelvic actinomycosis may vary between individuals, is often accompanied by complications, and is frequently misdiagnosed. Here, we report a case of pelvic actinomycosis, presenting as a huge pelvic mass and complicated by a vaginal fistula, a cutaneous fistula, and bilateral hydronephrosis, and we discuss the diagnosis and management of this patient. CASE REPORT: A 35-year-old woman was referred to our hospital with a huge pelvic complex mass and progressively worsening low abdominal pain. The tumor workup, which included a computed tomography (CT) scan, revealed an extended pelvic abscess and bilateral hydronephrosis. Both cutaneous and vaginal fistulas were also noted. Endometrial curettage and biopsies of the skin and vaginal lesions confirmed the diagnosis of actinomycosis. The patient underwent conservative treatment and recovered well, although the skin lesion only healed after 12 weeks of oral antibiotic treatment. At the 1-year follow-up, a CT scan showed sequelae including a mildly atrophic left kidney and left hydronephrosis. CONCLUSION: In patients presenting with a pelvic mass and an IUD in the uterine cavity, the diagnosis of actinomycosis should be seriously considered. A detailed workup, including a CT scan, endometrial curettage and biopsies where possible, should be performed before surgery. Once diagnosis has been confirmed, conservative medical treatment should be attempted before considering laparotomy, to reduce the risk of complications. Despite successful treatment with antibiotics, long-term sequelae such as hydronephrosis and renal atrophy are possible in cases of extended pelvic actinomycosis.