Prenatal detection of mosaicism for a genome wide uniparental disomy cell line in a cohort of patients: Implications and outcomes.

Objectives: To investigate the prenatal detection rate of mosaicism by SNP microarray analysis, in which an individual has not one, but two, complete genomes (sets of DNA) in their body, a normal biparental line with a Genome Wide Uniparental Disomy (GWUPD) cell line was used.

Methods: This study retrospectively examines the prenatal detection of GWUPD in a cohort of ∼90,000 prenatal specimens and ∼20,000 products of conceptions (POCs) that were studied by SNP microarray.

Results: In total, 25 cases of GWUPD were detected; 16 cases were detected prenatally with GWUPD (∼0.

A prenatal diagnosis of mosaic trisomy 5 reveals a postnatal complete uniparental disomy of chromosome 5 with multiple congenital anomalies.

Mosaic trisomy 5 is a very rare condition in liveborns, with few cases reported in the last four decades. There are some reports of prenatally diagnosed mosaic trisomy 5 resulting in phenotypically normal offspring, suggesting a low level of mosaicism, but there are also reports associated with multiple congenital anomalies, cardiovascular malformations, and intrauterine growth restriction. We report an infant male diagnosed with mosaic trisomy 5 (5/15 cells) via amniocentesis.

Chromosomal microarray analysis in clinical evaluation of neurodevelopmental disorders-reporting a novel deletion of SETDB1 and illustration of counseling challenge.

Background: The pathogenicity of copy number variations (CNV) in neurodevelopmental disorders is supported by research literature. However, few studies have evaluated the utility and counseling challenges of CNV analysis in clinic.

Methods: We analyzed the findings of CNV studies from a cohort referred for genetics evaluation of autism spectrum disorders (ASD), developmental disability (DD), and intellectual disability (ID).

Mosaic paternal genome-wide uniparental isodisomy with down syndrome.

We report on a 6-month-old girl with two apparent cell lines; one with trisomy 21, and the other with paternal genome-wide uniparental isodisomy (GWUPiD), identified using single nucleotide polymorphism (SNP) based microarray and microsatellite analysis of polymorphic loci. The patient has Beckwith-Wiedemann syndrome (BWS) due to paternal uniparental disomy (UPD) at chromosome location 11p15 (UPD 11p15), which was confirmed through methylation analysis. Hyperinsulinemic hypoglycemia is present, which is associated with paternal UPD 11p15.

Maternal uniparental isodisomy causing autosomal recessive GM1 gangliosidosis: a clinical report.

Uniparental disomy is a genetic cause of disease that may result in the inheritance of an autosomal recessive condition. A child with developmental delay and hypotonia was seen and found to have severely abnormal myelination. Lysosomal enzyme testing identified an isolated deficiency of beta-galactosidase.

Three cases of isolated terminal deletion of chromosome 8p without heart defects presenting with a mild phenotype.

Individuals with isolated terminal deletions of 8p have been well described in the literature, however, molecular characterization, particularly by microarray, of the deletion in most instances is lacking. The phenotype of such individuals falls primarily into two categories: those with cardiac defects, and those without. The architecture of 8p has been demonstrated to contain two inversely oriented segmental duplications at 8p23.

Phenotypic heterogeneity in a family with a small atypical microduplication of chromosome 22q11.2 involving TBX1.

The chromosome 22q11.2 region is commonly involved in non-allelic homologous recombination (NAHR) events. Microduplications of 22q11.

UPD detection using homozygosity profiling with a SNP genotyping microarray.

Single nucleotide polymorphism (SNP) based chromosome microarrays provide both a high-density whole genome analysis of copy number and genotype. In the past 21 months we have analyzed over 13,000 samples primarily referred for developmental delay using the Affymetrix SNP/CN 6.0 version array platform.

Microdeletion/microduplication of proximal 15q11.2 between BP1 and BP2: a susceptibility region for neurological dysfunction including developmental and language delay.

The proximal long arm of chromosome 15 has segmental duplications located at breakpoints BP1-BP5 that mediate the generation of NAHR-related microdeletions and microduplications. The classical Prader-Willi/Angelman syndrome deletion is flanked by either of the proximal BP1 or BP2 breakpoints and the distal BP3 breakpoint. The larger Type I deletions are flanked by BP1 and BP3 in both Prader-Willi and Angelman syndrome subjects.

Partial trisomy 19p13.3 and partial monosomy 1p36.3: Clinical report and a literature review.

We report on a 15-month-old girl with a deletion of the distal short arm of chromosome 1p36.3, partial trisomy of the short arm of chromosome 19p13.3, growth and developmental delay, and multiple anomalies including microcephaly, bifrontal prominence, obtuse frontonasal angle, short columella, hypertelorism, sacral dimples, and a bicuspid pulmonary valve.

Ovotesticular disorder of sexual development (true hermaphroditism).

Objectives: To determine the mechanism for the 46,XX/46,XY karyotype observed in a patient with an ovotesticular disorder of sexual development (ie, true hermaphroditism).

Methods: Cytogenetic, molecular cytogenetic, and molecular DNA analyses were performed on the blood, skin, and left and right gonadal tissue from 2 surgical procedures. The results of these studies were used to determine whether the ovotesticular disorder of sexual development resulted from mosaicism or tetragametic chimerism.