Diagnostic yield of array CGH in patients with autism spectrum disorder in Hong Kong.

Background: Chromosomal microarray offers superior sensitivity for identification of submicroscopic copy number variants (CNV) and it is advocated to be the first tier genetic testing for patients with autism spectrum disorder (ASD). In this regard, diagnostic yield of array comparative genomic hybridization (CGH) for ASD patients is determined in a cohort of Chinese patients in Hong Kong.

Methods: A combined adult and paediatric cohort of 68 Chinese ASD patients (41 patients in adult group and 27 patients in paediatric group).

A Fetus with Hb Bart's Disease Due to Maternal Uniparental Disomy for Chromosome 16.

We here report an unusual case of Hb Bart's (γ4) disease. Thalassemia screening of a couple showed that the wife was an α(0)-thalassemia (α(0)-thal) carrier and her husband's mean corpuscular volume (MCV) was normal. Chorionic villus sampling (CVS) was performed at 13 weeks' gestation for positive Down syndrome screening and chromosomal study of the cultured CVS showed a normal karyotype.

The clinical impact of chromosomal microarray on paediatric care in Hong Kong.

Objective: To evaluate the clinical impact of chromosomal microarray (CMA) on the management of paediatric patients in Hong Kong.

Methods: We performed NimbleGen 135k oligonucleotide array on 327 children with intellectual disability (ID)/developmental delay (DD), autism spectrum disorders (ASD), and/or multiple congenital anomalies (MCAs) in a university-affiliated paediatric unit from January 2011 to May 2013. The medical records of patients were reviewed in September 2013, focusing on the pathogenic/likely pathogenic CMA findings and their "clinical actionability" based on established criteria.

Under-recognition of 22q11.2 deletion in adult Chinese patients with conotruncal anomalies: implications in transitional care.

22q11.2 deletion syndrome (22q11.2DS) is a multi-systemic disorder with high phenotypic variability.

A prenatal case of split-hand malformation associated with 17p13.3 triplication - a dilemma in genetic counseling.

Copy number gain of 17p13.3 has been shown to be associated with developmental delay/autism and Split-Hand-Foot malformation. We report a case of fetus with bilateral split-hand malformation detected on prenatal ultrasound.

Two unusual cases of haemoglobin Bart's hydrops fetalis due to uniparental disomy or non-paternity.

The authors present 2 unusual cases of haemoglobin (Hb) Bart's hydrops fetalis and highlight the problem of a screening system for α-thalassaemia which focuses on maternal and paternal mean corpuscular volume (MCV) alone. Normal paternal MCV may not preclude fetal Hb Bart's disease because of the rare occurrence of maternal uniparental disomy or non-paternity. During a mid-trimester anomaly scan, with fetal cardiomegaly or hydrops in a woman with low MCV but normal paternal MCV, obstetricians should remain alert for fetal Hb Bart's disease.

Expanded Prader-Willi syndrome due to chromosome 15q11.2-14 deletion: report and a review of literature.

We report on a male infant with de novo unbalanced t(5;15) translocation resulting in a 17.23 Mb deletion within 15q11.2-q14 and a 25.

Noninvasive prenatal molecular karyotyping from maternal plasma.

Fetal DNA is present in the plasma of pregnant women. Massively parallel sequencing of maternal plasma DNA has been used to detect fetal trisomies 21, 18, 13 and selected sex chromosomal aneuploidies noninvasively. Case reports describing the detection of fetal microdeletions from maternal plasma using massively parallel sequencing have been reported.

Prospective assessment of the Hong Kong Hospital Authority universal Down syndrome screening programme.

Objective: To evaluate the performance of the locally developed universal Down syndrome screening programme.

Design: Population-based cohort study in the period July 2010 to June 2011 inclusive.

Setting: Four Hong Kong Hospital Authority Departments of Obstetrics and Gynaecology and a central university-based laboratory for maternal serum processing and risk determination.

Noninvasive prenatal diagnosis of fetal trisomy 18 and trisomy 13 by maternal plasma DNA sequencing.

Massively parallel sequencing of DNA molecules in the plasma of pregnant women has been shown to allow accurate and noninvasive prenatal detection of fetal trisomy 21. However, whether the sequencing approach is as accurate for the noninvasive prenatal diagnosis of trisomy 13 and 18 is unclear due to the lack of data from a large sample set. We studied 392 pregnancies, among which 25 involved a trisomy 13 fetus and 37 involved a trisomy 18 fetus, by massively parallel sequencing.

Non-invasive prenatal assessment of trisomy 21 by multiplexed maternal plasma DNA sequencing: large scale validity study.

Objectives: To validate the clinical efficacy and practical feasibility of massively parallel maternal plasma DNA sequencing to screen for fetal trisomy 21 among high risk pregnancies clinically indicated for amniocentesis or chorionic villus sampling.

Design: Diagnostic accuracy validated against full karyotyping, using prospectively collected or archived maternal plasma samples.

Setting: Prenatal diagnostic units in Hong Kong, United Kingdom, and the Netherlands.

Systematic identification of placental epigenetic signatures for the noninvasive prenatal detection of Edwards syndrome.

Background: Noninvasive prenatal diagnosis of fetal aneuploidy by maternal plasma analysis is challenging owing to the low fractional and absolute concentrations of fetal DNA in maternal plasma. Previously, we demonstrated for the first time that fetal DNA in maternal plasma could be specifically targeted by epigenetic (DNA methylation) signatures in the placenta. By comparing one such methylated fetal epigenetic marker located on chromosome 21 with another fetal genetic marker located on a reference chromosome in maternal plasma, we could infer the relative dosage of fetal chromosome 21 and noninvasively detect fetal trisomy 21.

Maternal serum anti-Mullerian hormone level is not superior to chronological age in predicting Down syndrome pregnancies.

Objective: To compare the difference in maternal serum anti-Mullerian hormone (AMH) level between Down syndrome pregnancies and unaffected pregnancies, and to evaluate its performance as a screening marker for Down syndrome pregnancy.

Method: A total of 145 pregnancies affected by foetal Down syndrome and 290 unaffected controls matched with maternal age and gestational age were selected, and their archived first or second trimester serum retrieved for AMH assay.

Results: There was no significant difference in maternal serum AMH level between pregnancies affected and unaffected by foetal Down syndrome.

Chromosomal anomalies and Y-microdeletions among Chinese subfertile men in Hong Kong.

Objective: To report the type and frequency of chromosomal anomalies and Y-microdeletions among Hong Kong Chinese subfertile men with sperm concentrations lower than 5 million/mL. DESIGN. Retrospective study.

Assessing discrepant findings between QF-PCR on uncultured prenatal samples and karyotyping on long-term culture.

Objective: To assess the prevalence of discrepant results found between quantitative fluorescent polymerase chain reaction (QF-PCR) analysis on uncultured prenatal samples and karyotyping on long-term culture.

Method: Results of QF-PCR from 1932 amniotic fluid (AF) and 1132 chorionic villus (CV) samples collected from September 1999 to February 2008 were analyzed. Nature of discrepancies was categorized for normal or abnormal results from uncultured and cultured samples.

Maternal plasma or human serum albumin in wash buffer enhances enrichment and ex vivo expansion of human umbilical cord blood CD34+ cells.

Umbilical cord blood is a valuable source of haemopoietic stem/progenitor cells (HSC) for transplantation. This study explored the effect of maternal plasma/human serum albumin (HSA) in the purification and culture conditions of CD34+ cells derived from human umbilical cord blood. During CD34+ cell enrichment, including maternal plasma or HSA instead of fetal bovine serum (FBS) in the wash buffer, significantly increased the purity and the fold expansion of CD34+ cells.

Semi-quantitative fluorescent PCR analysis identifies PRKAA1 on chromosome 5 as a potential candidate cancer gene of cervical cancer.

Objective: Comparative genomic hybridization has frequently detected amplification of chromosome 5p in cervical cancer, but candidate cancer genes within the region are rarely known. Therefore, we pursued to identify potential candidate gene related to cervical cancer development.

Methods: A series of 128 cervical tumor samples were examined by semi-quantitative fluorescent differential PCR for copy number changes on three candidate genes (PRKAA1, CTNND2 and POLS) mapped to chromosome 5p and one gene (ERBIN) mapped to chromosome 5q12.

Prenatal detection of a de novo Yqh-acrocentric translocation.

Objectives: To identify the extra chromosomal material on 46,XX,21p+ for prenatal diagnosis.

Design And Methods: Conventional cytogenetic studies using GTG (G bands by trypsin using Giemsa) and CBG (C bands by barium hydroxide using Giemsa) techniques were performed on chromosomes at metaphase obtained from cultured amniocytes and parental blood lymphocytes. Molecular cytogenetic techniques, QF-PCR (quantitative fluorescent polymerase chain reaction), FISH (fluorescent in-situ hybridization), and DA-DAPI (Distamycin A and 4,6-diamino-2-phenylindole) staining, were then used to clarify the extra material present on fetal chromosome 21 p.

Simple non-invasive prenatal detection of Hb Bart's disease by analysis of fetal erythrocytes in maternal blood.

Objective: To investigate a simple non-invasive technique for early detection of Hemoglobin (Hb) Bart's disease.

Method: Maternal blood smears from 8 known Hb Bart's pregnancies and 40 at-risk pregnancies were investigated. Maternal peripheral blood smears were stained with fluorescence-labeled monoclonal antibodies against alpha- and embryonic zeta-globin chains.

Genetic abnormalities and HPV status in cervical and vulvar squamous cell carcinomas.

Cervical and vulvar cancers are diseases of the female lower genital tract, and high-risk human papillomavirus (HPV) infection is the most important risk factor for the development of both cancers. However, it is clear that additional genetic events are necessary for tumor progression, particularly in HPV-negative cases. We detected the presence of high-risk HPV16 and HPV18 genomes by gene-specific polymerase chain reaction and searched for common genetic imbalances by comparative genomic hybridization (CGH) in 28 cervical and 8 vulvar tumor samples and 7 cancer cell lines.

Rapid aneuploidy screening (FISH or QF-PCR): the changing scene in prenatal diagnosis?

The accuracy of new molecular diagnostics, fluoresence in situ hybridization or quantitative fluorescence-PCR (collectively known as rapid aneuploidy screening), in prenatal diagnosis has already been demonstrated in a number of large studies. The challenge now is how to apply them clinically in the most cost-effective manner. It is now time to appraise whether rapid aneuploidy screening can replace traditional karyotyping when amniocenteses are performed for increased risk of Down's syndrome by maternal serum screening or advanced maternal age in the absence of ultrasound abnormality.