Liang-Kai Wang

Chromosome 17p13.3 deletion syndrome: aCGH characterization, prenatal findings and diagnosis, and literature review.

We report a molecular cytogenetic characterization of 17p13.3 deletion syndrome by array comparative genomic hybridization (aCGH), fluorescence in situ hybridization (FISH) and quantitative polymerase chain reaction (qPCR) in a fetus with lissencephaly, corpus callosum dysgenesis, ventriculomegaly, microcephaly, intrauterine growth restriction (IUGR), polyhydramnios and single umbilical artery. aCGH analysis revealed a 3.17-Mb deletion at 17p13.3, or arr [hg19] 17p13.3 (0-3,165,530)×1. The qPCR assays revealed a maternal origin of the deletion. Metaphase FISH analysis detected the absence of the LIS1 probe signal on the aberrant chromosome 17. The karyotype was 46,XX,del(17)(p13.3). We review the literature of chromosome 17p13.3 deletion syndrome with prenatal findings and diagnosis, and suggest that prenatal ultrasound detection of central nervous system anomalies such as lissencephaly, corpus callosum dysgenesis/agenesis, ventriculomegaly and microcephaly associated with IUGR, polyhydramnios, congenital heart defects, abdominal wall defects and renal abnormalities should include a differential diagnosis of chromosome 17p13.3 deletion syndrome.

3q26.31-q29 duplication and 9q34.3 microdeletion associated with omphalocele, ventricular septal defect, abnormal first-trimester maternal serum screening and increased nuchal translucency: prenatal diagnosis and aCGH characterization.

We present prenatal diagnosis and array comparative genomic hybridization characterization of 3q26.31-q29 duplication and 9q34.3 microdeletion in a fetus with omphalocele, ventricular septal defect, increased nuchal translucency, abnormal first-trimester maternal screening and facial dysmorphism with distinct features of the 3q duplication syndrome and Kleefstra syndrome. The 26.61-Mb duplication of 3q26.31-q29 encompasses EPHB3, CLDN1 and CLDN16, and the 972-kb deletion of 9q34.3 encompasses EHMT1. We review the literature of partial trisomy 3q associated with omphalocele and discuss the genotype-phenotype correlation in this case.

Spontaneous rupture and massive hemoperitoneum from uterine leiomyomas and adenomyosis in a nongravid and unscarred uterus.

Uterine leiomyomas (fibroids or myomas) are benign monoclonal tumors arising from the smooth muscle cells of the myometrium [1]. The symptoms attributed to myomas include heavy or prolonged menstrual bleeding, pelvic pressure and pain, and reproductive dysfunction. Acute or chronic pelvic pain may be a result of mass bulk-related symptoms, dysmenorrhea, dyspareunia, or degeneration or torsion of the myoma [2]. Adenomyosis refers to a disorder in which endometrial glands and stroma are present within the uterine musculature (uterine adenomyomatosis). Heavy menstrual bleeding, painful menstruation, and chronic pelvic pain are the major symptoms of adenomyosis, and they occur in approximately 25% of cases [3]. Although leiomyomas and adenomyosis are common gynecological disorders, hemorrhage, internal bleeding, hemoperitoneum, and uterine rupture due to these disease etiologies are rare and can easily be missed in emergency conditions. Furthermore, delayed diagnosis and management may increase the risk of morbidity andmortality [4,5]. Herein, we report an extremely rare case presenting as spontaneous rupture from uterine leiomyomas with adenomyosis in a nongravid and unscarred uterus. A 39-year-old female presented to our emergency department in shock and near fainting condition accompanied with acute diffuse lower abdomen pain. Her medical history was unremarkable, and she denied undergoing any surgery such as laparoscopy or laparotomy for uterine tumors. She denied being pregnant, having given birth, or undergoing an abortion in the past and denied having an

The reliability of transabdominal cervical length measurement in a low-risk obstetric population: Comparison with transvaginal measurement.

OBJECTIVE To determine the correlation between transabdominal (TA) and transvaginal (TV) cervical length measurement in a low-risk obstetric population in Taiwan. MATERIALS AND METHODS Women with a singleton pregnancy between 20 weeks and 24 weeks of gestation underwent postvoid TA and TV cervical length measurements. Differences between the measurements obtained using the two methods were evaluated. RESULTS Two hundred and five women agreed to participate in the study. Paired TA and TV measurements were obtained in 174 women. The mean TA cervical length was 36.0 ± 4.9 mm and the mean TV cervical length was 37.6 ± 5.4 mm. The mean TA cervical length was shorter than the mean TV cervical length by 1.6 mm. The 5(th) percentile of TA and TV cervical length was 29 mm and 29.1 mm, respectively. The discrepancies between the two methods were not significantly correlated with maternal body mass index (BMI). All women with TV cervical length <25 mm had a corresponding TA cervical length <29 mm. CONCLUSION The TA cervical length could be obtained in the majority of the low-risk pregnant women in the present study, and the TA cervical length was closely correlated with the TV cervical length. The use of TA ultrasound could be an effective initial tool for cervical length screening in low-risk pregnant women. TA cervical length <29 mm (5(th) percentile) could be used as a cut-off value for further TV ultrasound.

First-trimester diagnosis of recurrent omphalocele associated with fetal trisomy 18 but without parental mosaicism

a Department of Obstetrics and Gynecology, Mackay Memorial Hospital, Taipei, Taiwan b Department of Medical Research, Mackay Memorial Hospital, Taipei, Taiwan c Department of Biotechnology, Asia University, Taichung, Taiwan d School of Chinese Medicine, College of Chinese Medicine, China Medical University, Taichung, Taiwan e Institute of Clinical and Community Health Nursing, National Yang-Ming University, Taipei, Taiwan f Department of Obstetrics and Gynecology, School of Medicine, National Yang-Ming University, Taipei, Taiwan g Department of Obstetrics and Gynecology, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung, Taiwan h Department of Bioengineering, Tatung University, Taipei, Taiwan

Fetoplacental cytogenetic discrepancy in a pregnancy with fetal mosaic tetrasomy 12p and Pallister–Killian syndrome detected by amniocentesis

OBJECTIVE We present fetoplacental cytogenetic discrepancy in a pregnancy with prenatally detected mosaic tetrasomy 12p by amniocentesis. CASE REPORT A 34-year-old woman underwent amniocentesis at 17 weeks of gestation because of advanced maternal age. Cytogenetic analysis of cultured amniocytes revealed a karyotype of 47,XX,+i(12)(p10)[7]/46,XX[16]. Array comparative genomic hybridization (aCGH) analysis of the DNA extracted from cultured amniocytes revealed arr (12p)×3, (X)×2. Prenatal ultrasound findings were unremarkable. The pregnancy was subsequently terminated, and a fetus was delivered with facial dysmorphism consistent with the clinical features of Pallister-Killian syndrome (PKS). Postnatal cytogenetic analysis of the cultured cells from umbilical cord, skin, cord blood and placenta revealed 47,XX,+i(12)(p10)[6]/46,XX[34] in umbilical cord, 47,XX,+i(12)(p10)[11]/46,XX[29] in skin, 47,XX,+i(12)(p10)[3]/46,XX[47] in cord blood and 46,XX[40] in placenta. The mosaic tetrasomy 12p levels of the umbilical cord, skin, cord blood and placenta were 15%, 27.5%, 6% and 0%, respectively. aCGH analysis of the DNA extracted from uncultured cord blood and placenta revealed arr 12p13.33p11.1 (230,421-34,756,209)×3.0 in cord blood but no genomic imbalance in placenta. Polymorphic DNA marker analysis showed a maternal origin of the supernumerary isochromosome 12p in cord blood but biparental inheritance with equal fluorescent activity in placenta. CONCLUSION Pregnancy with fetal PKS and mosaic tetrasomy 12p may present fetoplacental cytogenetic discrepancy. Therefore, genetic analysis on placenta alone may fail to detect fetal mosaic tetrasomy 12p associated with PKS.

Second-trimester plasma mannose-binding lectin levels and risk of preterm birth

Abstract Objective: To investigate whether mannose-binding lectin (MBL) gene polymorphisms and low levels of second-trimester plasma MBL were significant risk factors for preterm birth in Taiwanese women. Methods: We conducted a prospective longitudinal study to explore the associations of MBL2 gene single nucleotide polymorphisms and plasma MBL levels between preterm birth and term controls. Blood samples were collected at 16–23 weeks of gestation, and were divided into 51 mothers with preterm births and 255 term controls after delivery. Blood samples were further collected at delivery from 11 mothers with term delivery and 9 with preterm births. DNA was isolated, and polymorphisms in exon 1, the promoter untranslated regions of MBL2 were determined by polymerase chain reaction. The plasma concentrations of MBL were measured by enzyme-linked immunosorbent assay. Results: There is a positive correlation between SNP genotypes and second-trimester plasma MBL levels. Among mothers with preterm births, a higher frequency of specific genotypes with low MBL levels was not observed. The second-trimester plasma MBL levels were not significantly different between mothers with preterm births (N = 51) and term deliveries (N = 255). However, among mothers (N = 11) with term pregnancies, the MBL plasma level significantly increased from the second trimester to delivery, whereas in mothers (N = 9) who developed preterm delivery, the MBL level did not significantly change. Conclusion: Genotypes associated with low levels of plasma MBL during pregnancy did not increase the risk of preterm births. A low second-trimester plasma MBL level is therefore not a predictor for the development of preterm birth.

Prenatal diagnosis and molecular cytogenetic characterization of chromosome 22q11.2 deletion syndrome associated with congenital heart defects

OBJECTIVE To report prenatal diagnosis of 22q11.2 deletion syndrome in a pregnancy with congenital heart defects in the fetus. CASE REPORT A 26-year-old, primigravid woman was referred for counseling at 24 weeks of gestation because of abnormal ultrasound findings of fetal congenital heart defects. The Level II ultrasound revealed a singleton fetus with heart defects including overriding aorta, small pulmonary artery, and ventricular septal defect. Cordocentesis was performed. The DNA extracted from the cord blood was analyzed by multiplex ligation-dependent amplification (MLPA). The MLPA showed deletion in the DiGeorge syndrome (DGS) critical region of chromosome 22 low copy number repeat (LCR) 22-A∼C. Conventional cytogenetic analysis revealed a normal male karyotype. Repeated amniocentesis and cordocentesis were performed. Whole-genome array comparative genomic hybridization (aCGH) on cord blood was performed. aCGH detected a 3.07-Mb deletion at 22q11.21. Conventional cytogenetic analysis of cultured amniocytes revealed a karyotype 46,XY. Metaphase fluorescence in situ hybridization (FISH) analysis on cultured amniocytes confirmed an interstitial 22q11.2 deletion. CONCLUSION Prenatal ultrasound findings of congenital heart defects indicate that the fetuses are at increased risk for chromosome abnormalities. Studies for 22q11.2 deletion syndrome should be considered adjunct to conventional karyotyping. Although FISH has become a standard procedure for diagnosis of 22q11.2 deletion syndrome, MLPA can potentially diagnose a broader spectrum of abnormalities, and aCGH analysis has the advantage of refining the 22q11.2 deletion breakpoints and detecting uncharacterized chromosome rearrangements or genomic imbalances.

Molecular cytogenetic characterization and prenatal diagnosis of familial Xp22.33 microdeletion encompassing short stature homeobox gene in a male fetus with a favorable outcome

a Department of Obstetrics and Gynecology, MacKay Memorial Hospital, Taipei, Taiwan b Department of Medical Research, MacKay Memorial Hospital, Taipei, Taiwan c Department of Biotechnology, Asia University, Taichung, Taiwan d School of Chinese Medicine, College of Chinese Medicine, China Medical University, Taichung, Taiwan e Institute of Clinical and Community Health Nursing, National Yang-Ming University, Taipei, Taiwan f Department of Obstetrics and Gynecology, School of Medicine, National Yang-Ming University, Taipei, Taiwan g Genephile Bioscience Laboratory, Kos Obstetrics and Gynecology, Taipei, Taiwan h Department of Pediatrics, MacKay Memorial Hospital, Taipei, Taiwan i Department of Medicine, MacKay Medical College, New Taipei City, Taiwan j Department of Early Childhood Care, National Taipei University of Nursing and Health Sciences, Taipei, Taiwan k Gene Biodesign Co. Ltd, Taipei, Taiwan l Department of Bioengineering, Tatung University, Taipei, Taiwan

Molecular genetic characterization of a prenatally detected 1.484-Mb Xq13.3-q21.1 duplication encompassing ATRX and a literature review of syndromic intellectual disability and congenital abnormalities in males with a duplication at Xq13.3-q21.1

OBJECTIVE We present prenatal diagnosis of dup(X)(q13.3q21.1) in a male fetus and molecular genetic analysis in three generations and a literature review of syndromic intellectual disability and congenital abnormalities in males with a duplication at Xq13.3-q21.1. CASE REPORT A 35-year-old, primigravid woman underwent amniocentesis at 18 weeks of gestation because of advanced maternal age. The woman and her mother were phenotypically normal, and there was no intellectual disability in the maternal family. Cytogenetic analysis of cultured amniocytes revealed a karyotype of 46,XY. Simultaneous array comparative genomic hybridization (aCGH) analysis on uncultured amniotic fluid incidentally detected a 1.484-Mb microduplication of Xq13.3-q21.1 encompassing ATRX. Subsequent aCGH analysis on fetal blood, maternal blood and grandmothers blood revealed the same 1.484-Mb dup(X)(q13.3q21.1). Prenatal ultrasound findings were unremarkable with no growth restriction and no short stature. After genetic counseling of syndromic intellectual disability in males with ATRX duplication, the woman elected to terminate the pregnancy. The fetus postnatally manifested hypoplastic male external genitalia, clinodactyly, hypertelorism, midface hypoplasia, epicanthic folds and micrognathia. CONCLUSION Simultaneous aCGH analysis on uncultured amniotic fluid in addition to conventional cytogenetics at amniocentesis is practical and may help in detecting unknown familial inheritance of subtle X chromosome aberrations.