Genetic investigations of autosomal recessive inherited ichthyosis impressed by fetal ultrasound: Exome sequencing and haplotype linkage analysis.

Objective: Ichthyosis are complex skin diseases, characterized by hyperkeratosis with various degrees of thickening, desquamation, and erythema. The prenatal diagnosis of ichthyosis is challenged due to the clinical and genetic heterogeneity and the late-onset of fetal features on ultrasound scan. Here, we reported two fetuses with Harlequin ichthyosis (HI), a severe subtype of autosomal recessive congenital ichthyosis (ARCI), who were diagnosed prenatally by images and genetic investigations.

De Novo Noninversion Variants Implicated in Sporadic Hemophilia A: A Variant Origin and Timing Study.

Sporadic hemophilia A (HA) enables the persistence of HA in the population. gene inversion originates mainly in male germ cells during meiosis. To date, no studies have shown the origin and timing of HA sporadic noninversion variants (NIVs); herein, we assume that HA-sporadic NIVs are generated as a de novo variant.

Skewed X-Chromosome Inactivation and Parental Gonadal Mosaicism Are Implicated in X-Linked Recessive Female Hemophilia Patients.

Background: Hemophilia A (HA) and B (HB) are X-linked recessive disorders that mainly affect males born from a mother carrier. Females are rarely affected but a number of mechanisms have been suggested in symptomatic females, such as skewed X-chromosome inactivation (XCI), chromosomal rearrangements, and hermaphrodites. Different methodologies are required to elucidate the underlying causes of such diseases in female patients.

Proposal for Practical Approach in Prenatal Diagnosis of Beckwith-Wiedemann Syndrome and Review of the Literature.

Background: Beckwith-Wiedemann syndrome (BWS) is a phenotypically and genetically heterogeneous disorder associated with epigenetic/genetic aberrations on chromosome 11p15.4p15.5.

Genome-Wide Microarray Analysis Suggests Transcriptomic Response May Not Play a Major Role in High- to Low-Altitude Acclimation in Harvest Mouse ().

The harvest mouse () is a small rodent species with a wide range of vertical distribution in Taiwan, extending from the sea level to 3100 m altitude. This species has recently suffered from habitat loss in high-altitude areas due to orchard cultivation, which may have resulted in mouse migration from high to low altitude. To investigate whether there is any physiological mechanism involved in altitude acclimation, rat cDNA microarray was used to compare transcriptomic patterns of the skeletal muscle tissues taken from individuals native to the high-altitude environment and those transferred to the low-altitude captive site.

Application of molecular cytogenetic techniques to characterize the aberrant Y chromosome arising de novo in a male fetus with mosaic 45,X and solve the discrepancy between karyotyping, chromosome microarray, and multiplex ligation dependent probe amplification.

We present a rare male fetus with karyotype of mosaic 45,X that comprises two types of aberrant Y chromosomes arising de novo (Yq12 deletion and isodicentric Yq11.22). Both types of the aberrant Y chromosomes lack the AZFc region which are expected to result in oligospermia but unaffected male external genitalia.

Noninvasive prenatal diagnosis of fetal aneuploidy by circulating fetal nucleated red blood cells and extravillous trophoblasts using silicon-based nanostructured microfluidics.

Background: Noninvasive prenatal testing (NIPT) based on cell-free DNA in maternal circulation has been accepted worldwide by the clinical community since 2011 but limitations, such as maternal malignancy and fetoplacental mosaicism, preclude its full replacement of invasive prenatal diagnosis. We present a novel silicon-based nanostructured microfluidics platform named as "Cell Reveal™" to demonstrate the feasibility of capturing circulating fetal nucleated red blood cells (fnRBC) and extravillous cytotrophoblasts (EVT) for cell-based noninvasive prenatal diagnosis (cbNIPD).

Methods: The "Cell Reveal™" system is a silicon-based, nanostructured microfluidics using immunoaffinity to capture the trophoblasts and the nucleated RBC (nRBC) with specific antibodies.

Genomic analyses of the Formosan harvest mouse (Micromys minutus) and comparisons to the brown Norway rat (Rattus norvegicus) and the house mouse (Mus musculus).

The harvest mouse, Micromys minutus (MMIN), has a very wide range of distribution (from the British Isles across the Euroasian continent to Japan and Taiwan). We studied an isolated population of MMIN in Taiwan, which is at the southeastern margin of the species' geographic distribution, and compared its genetic complement with those of the same species previously reported from other geographic locations and with two model rodent species, the house mouse (Mus musculus) and the brown Norway rat (Rattus norvegicus). The diploid number (2N) of MMIN was 68, consistent with that reported for other populations.

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

Objective: To present prenatal diagnosis and molecular cytogenetic characterization of mosaicism for a small supernumerary marker chromosome (sSMC) derived from ring chromosome 2 [r(2)].

Methods And Results: A 35-year-old woman underwent amniocentesis at 17 weeks of gestation, because of advanced maternal age. Amniocentesis revealed a de novo ring-shaped sSMC in 11 of 23 colonies of cultured amniocytes.

Use of a cytogenetic whole-genome comparison to resolve phylogenetic relationships among three species: implications for mammalian systematics and conservation biology.

The objective was to apply a novel modification of a genome-wide, comparative cytogenetic technique (comparative genomic hybridization, comparative genomic hybridization (CGH)), to study species belonging to the myrmecophagous (ant/termite eating) mammalian orders/superorders (Pholidota, Tubulidentata, Carnivora, and Xenarthra), as a model for other applications in mammalian systematics and conservation biology. In this study, CGH was applied to high-quality metaphase spreads of pangolin (Pholidota), using probes of sloth and canine (Xenarthra and Carnivora, respectively) genomic DNA labeled with different fluorophores, thereby facilitating analysis of the visible color spectrum on pangolin karyotypes. Our results posited that pholidotes are closer to carnivores than to xenarthrans, which confirmed the current consensus that myrmecophagy in these mammalian lineages was more likely because of homoplasy (convergent evolution) than being an ancestral character.

Prenatal diagnosis and molecular cytogenetic characterization of de novo partial trisomy 7p (7p15.3→pter) and partial monosomy 13q (13q33.3→qter) associated with Dandy-Walker malformation, abnormal skull development and microcephaly.

Objective: To present the prenatal diagnosis and molecular cytogenetic characterization of de novo partial trisomy 7p (7p15.3→pter) and partial monosomy 13q (13q33.3→qter) associated with Dandy-Walker malformation (DWM), abnormal skull development, microcephaly and multiple congenital anomalies.

Molecular delineation of the Y-borne Sry gene in the Formosan pangolin (Manis pentadactyla pentadactyla) and its phylogenetic implications for Pholidota in extant mammals.

The systematic status of Pholidota has been a matter of debate, particularly regarding the apparent inconsistency between morphological and molecular studies. The Sry gene, a master regulator of male sex determination in eutherian mammals, has not yet been used for phylogenetic analyses of extant mammals. The objective of the present study was to clone and characterize the complete gene (1300 base pairs; bp) and amino acid sequences (229 residues) of Sry from the Formosan pangolin (Manis pentadactyla pentadactyla), a member of Pholidota.

Complex rearrangements between chromosomes 6, 10, and 11 with multiple deletions at breakpoints.

Here we report on a girl with minor facial anomalies, cleft palate, seizures, microcephaly, psychomotor retardation, and a congenital heart defect. Complex of cytogenetic methods [GTG-banding, spectral karyotyping (SKY), fluorescence in situ hybridization (FISH), multicolor banding (mBAND), and comparative genomic hybridization (array CGH)] showed complex chromosomal rearrangements (CCRs) involving chromosomes 6, 10, and 11 and 4 deletions at the breakpoints. Her father had an unrelated translocation between chromosomes 3 and 16, suggesting the possibility of an autosomal dominant trait that predisposes to complex synapses and recombination between multiple chromosomes during meiosis.

Interstitial deletion 13q31 associated with normal phenotype: cytogenetic study of a family with concomitant segregation of reciprocal translocation and interstitial deletion.

Gain or loss of a fragment in human chromosomes has been associated with abnormal phenotypes in numerous genetic disorders. However, it is also possible that lack or excess of a particular chromosomal segment is a neutral polymorphism among populations and thus does not cause obvious abnormal phenotype. In this study, conventional GTG-banded karyotyping and molecular cytogenetic analyses (including fluorescence in situ hybridization, spectral karyotyping and comparative genomic hybridization) were applied to study the genotype-phenotype correlation in a Taiwanese family, in which a concomitant segregation of del(13)(q31q31) interstitial deletion and t(13;18)(q32;p11.

Comparison of immunohistochemical and fluorescence in situ hybridization assessment for HER-2/neu status in Taiwanese breast cancer patients.

Objective: Accurate diagnostic assessment of human epidermal growth factor receptor-2 (HER-2) is essential and a prerequisite for appropriate application of the humanized anti-HER-2 monoclonal antibody trastuzumab (Herceptin) to the treatment of patients with breast cancer. Immunohistochemistry (IHC) is the most widely applicable diagnostic modality in studying HER-2 status. Fluorescence in situ hybridization (FISH) is also recognized as a modality in cases with an equivocal IHC status (score, 2+).