Cytogenetic analysis in fetuses with late onset abnormal sonographic findings.

Objective: To determine the rate of chromosomal cytogenetic abnormalities in fetuses with late onset abnormal sonographic findings.

Design: Retrospective cohort of women who underwent amniocentesis at or beyond 23 weeks of gestation, for fetal karyotype and chromosomal microarray analysis, indicated due to late onset abnormal sonographic findings.

Results: All 103 fetuses had a normal karyotype.

When genotype is not predictive of phenotype: implications for genetic counseling based on 21,594 chromosomal microarray analysis examinations.

PurposeTo compare the frequency of copy-number variants (CNVs) of variable penetrance in low-risk and high-risk prenatal samples and postnatal samples.MethodsTwo cohorts were categorized according to chromosomal microarray analysis (CMA) indication: group I, low-risk prenatal-women with uneventful pregnancy (control group); group II, high-risk prenatal-women whose fetuses had congenital malformations; and group III, postnatal-individuals with unexplained developmental delay/intellectual disability, autism spectrum disorders, or multiple congenital anomalies. CNVs were categorized based on clinical penetrance: (i) high (>40%), (ii) moderate (10-40%), and (iii) low (<10%).

Cut-off value of nuchal translucency as indication for chromosomal microarray analysis.

Objectives: An association between isolated, increased nuchal translucency thickness (NT) and pathogenic findings on chromosomal microarray analysis (CMA) has been reported. A recent meta-analysis reported that most studies use a NT cut-off value of 3.5 mm.

Chromosomal microarray analysis in fetuses with aberrant right subclavian artery.

Objective: To evaluate the association between aberrant right subclavian artery (ARSA), with or without additional risk factors for aneuploidy or ultrasound abnormality, and results of chromosomal microarray analysis (CMA).

Methods: This was a multicenter study of fetuses diagnosed with ARSA that underwent genetic analysis by CMA, all samples being analyzed in the same laboratory. Clinical investigation included nuchal translucency measurement, first- and second-trimester maternal serum screening, early and late second-trimester fetal anatomy scans and fetal echocardiography.

Acute promyelocytic leukemia with isochromosome 17q and cryptic PML-RARA successfully treated with all-trans retinoic acid and arsenic trioxide.

Acute promyelocytic leukemia (APL) is a subtype of acute leukemia that is characterized by typical morphology, bleeding events and distinct chromosomal aberrations, usually the t(15;17)(q22;q21) translocation. Approximately 9% of APL patients harbor other translocations involving chromosome 17, such as the t(11;17)(q23;q21), t(5;17)(q35;q12-21), t(11;17)(q13;q21), and der(17). All-trans retinoic acid (ATRA) and arsenic trioxide (ATO) have specific targeted activities against the PML-RARA fusion protein.

A de-novo interstitial microduplication involving 2p16.1-p15 and mirroring 2p16.1-p15 microdeletion syndrome: Clinical and molecular analysis.

Background: Microdeletions of various sizes in the 2p16.1-p15 chromosomal region have been grouped together under the 2p16.1-p15 microdeletion syndrome.

Abnormal brain magnetic resonance imaging in two patients with Smith-Magenis syndrome.

Smith-Magenis syndrome (SMS) is a clinically recognizable contiguous gene syndrome ascribed to an interstitial deletion in chromosome 17p11.2. Seventy percent of SMS patients have a common deletion interval spanning 3.

Familial hydrocephalus with normal cognition and distinctive radiological features.

Hydrocephalus is a clinically and genetically heterogeneous condition. Individuals with posterior fossa abnormalities have an increased risk of developing hydrocephalus. The Dandy-Walker malformation, Dandy-Walker variant, and mega-cisterna magna (MCM) seem to represent a continuum of developmental anomalies of the posterior fossa.

Microdeletion syndromes disclose replication timing alterations of genes unrelated to the missing DNA.

Background: The temporal order of allelic replication is interrelated to the epigenomic profile. A significant epigenetic marker is the asynchronous replication of monoallelically-expressed genes versus the synchronous replication of biallelically-expressed genes. The present study sought to determine whether a microdeletion in the genome affects epigenetic profiles of genes unrelated to the missing segment.

Segmentation and classification of dot and non-dot-like fluorescence in situ hybridization signals for automated detection of cytogenetic abnormalities.

Signal segmentation and classification of fluorescence in situ hybridization (FISH) images are essential for the detection of cytogenetic abnormalities. Since current methods are limited to dot-like signal analysis, we propose a methodology for segmentation and classification of dot and non-dot-like signals. First, nuclei are segmented from their background and from each other in order to associate signals with specific isolated nuclei.

On the classification of a small imbalanced cytogenetic image database.

Solving a multiclass classification task using a small imbalanced database of patterns of high dimension is difficult due to the curse-of-dimensionality and the bias of the training toward the majority classes. Such a problem has arisen while diagnosing genetic abnormalities by classifying a small database of fluorescence in situ hybridization signals of types having different frequencies of occurrence. We propose and experimentally study using the cytogenetic domain two solutions to the problem.

Association of the low-activity COMT 158Met allele with ADHD and OCD in subjects with velocardiofacial syndrome.

Velocardiofacial syndrome (VCFS) is caused by a microdeletion in chromosome 22 and is a risk factor for the development of schizophrenia and other psychiatric disorders. The catechol-O-methyltransferase (COMT), residing in the 22q11.2 microdeletion region, is a major candidate gene for genetic susceptibility to neuropsychiatric disorders in VCFS.

Obsessive-compulsive disorder in patients with velocardiofacial (22q11 deletion) syndrome.

The study of neurogenetic microdeletion syndromes provides an insight into the developmental psychopathology of psychiatric disorders. The aim of the study was to evaluate the prevalence of psychiatric disorders, especially obsessive-compulsive disorder (OCD), in patients with velocardiofacial syndrome (VCFS), a 22q11 microdeletion syndrome. Forty-three subjects with VCFS of mean age 18.

Phenotypic expression of tissue mosaicism in a 45,X/46,X,dicY(q11.2) female.

We describe a girl who presented at the age of 11 years with short stature. She had female external genitalia and some clinical features of Turner syndrome. At laparotomy a uterus and Fallopian tubes and small gonad-like tissue masses in the region of the Fallopian fimbria were found.

FISH-detected delay in replication timing of mutated FMR1 alleles on both active and inactive X-chromosomes.

X-chromosome inactivation and the size of the CGG repeat number are assumed to play a role in the clinical, physical, and behavioral phenotype of female carriers of a mutated FMR1 allele. In view of the tight relationship between replication timing and the expression of a given DNA sequence, we have examined the replication timing of FMR1 alleles on active and inactive X-chromosomes in cell samples (lymphocytes or amniocytes) of 25 females: 17 heterozygous for a mutated FMR1 allele with a trinucleotide repeat number varying from 58 to a few hundred, and eight homozygous for a wild-type allele. We have applied two-color fluorescence in situ hybridization (FISH) with FMR1 and X-chromosome alpha-satellite probes to interphase cells of the various genotypes: the alpha-satellite probe was used to distinguish between early replicating (active) and late replicating (inactive) X-chromosomes, and the FMR1 probe revealed the replication pattern of this locus.

Replication timing of the various FMR1 alleles detected by FISH: inferences regarding their transcriptional status.

Following the application of two-color fluorescence in-situ hybridization (FISH) to human interphase cells, we examined the replication timing of the fragile-X locus relative to the non-transcribed late replicating alpha-satellite region of chromosome-X, a built-in intracellular reference locus. In this assay, an unreplicated locus is identified by a single hybridization signal (singlet; S), whereas a replicated locus is identified by a duplicated signal (doublet; D). Hence, following simultaneous hybridization with the FMR1 and alpha-satellite probes, male cells with one singlet and one doublet signal per cell (SD cells) indicate S-phase cells where only one of the two loci has replicated.