Use of array comparative genomic hybridization for prenatal diagnosis of fetuses with sonographic anomalies and normal metaphase karyotype.

Objective: To prospectively study the addition of array comparative genomic hybridization (CGH) to the prenatal evaluation of fetal structural anomalies.

Methods: Pregnant women carrying fetuses with a major structural abnormality were recruited at the time of invasive procedure for chromosome analysis. Only women whose fetuses had a normal karyotype (n = 50) were subsequently evaluated by array CGH using one of two arrays (1887 clones covering 622 loci or subsequently 4685 clones covering 1500 loci).

An instructive case of an 8-year-old boy with intellectual disability.

A child with global developmental delay sparing motor skills evolving into later intellectual disability with a consistently normal neuromuscular examination was discovered to have a dystrophin specific mutation in the 3' end of the gene. The deletion in the DMD gene was unsuspected and discovered through array comparative genomic hybridization and confirmed on polymerase chain reaction analysis. This case shows a central nervous system-specific and restrictive phenotype for a disorder that is conceptualized as being progressively neuromuscular in clinical expression.

In the middle of it all: a centered approach to chromosome analysis.

Background: The pericentromeric areas immediately flanking the centromeres are prone to instability owing to their high levels of repetitive sequences. This genomic instability makes the pericentromeric regions ideal candidates for the investigation of chromosomal abnormalities resulting in genetic disease. However, it is this instability that confounds attempts to analyze these regions of the genome.

Development of a high-density pericentromeric region BAC clone set for the detection and characterization of small supernumerary marker chromosomes by array CGH.

Purpose: Small supernumerary marker chromosomes are centric chromosomal segments that, by definition, cannot be characterized unambiguously by conventional chromosome banding. Marker chromosomes are of particular interest in clinical cytogenetics because they are nearly 10 times more frequent in individuals with mental retardation (0.426%) than in the normal population (0.

Detection of low-level mosaicism by array CGH in routine diagnostic specimens.

The advent of microarray-based comparative genomic hybridization (array CGH) promises to revolutionize clinical cytogenetics because of its ability to rapidly screen the genome at an unprecedented resolution. Yet, the ability of array CGH to detect and evaluate low-level mosaicism is not known. Our laboratory has analyzed over 3,600 clinical cases with the SignatureChip which we developed for the detection of microdeletions, microduplications, aneuploidy, unbalanced translocations, and subtelomeric and pericentromeric copy number alterations.

Targeted genomic microarray analysis for identification of chromosome abnormalities in 1500 consecutive clinical cases.

Objective: To assess the yield of array-based comparative genomic hybridization.

Study Design: The results of array comparative genomic hybridization were collected on 1500 consecutive clinical cases sent to our laboratory for a variety of developmental problems. Confirmation fluorescence in situ hybridization of metaphase or interphase cells, depending on the aberration, was performed.

Detecting sex chromosome anomalies and common triploidies in products of conception by array-based comparative genomic hybridization.

Objectives: In recent years, array-based comparative genomic hybridization (array CGH) has moved to the forefront of molecular cytogenetics with its ability to rapidly characterize chromosome abnormalities at resolutions much higher than routine chromosome banding. However, array CGH, like all CGH procedures, has heretofore been deemed unable to detect ploidy, a major cause of fetal demise and spontaneous miscarriage.

Method: We recently developed a CGH microarray that is designed for detecting aneuploidy and unbalanced chromosome rearrangements.

Use of targeted array-based CGH for the clinical diagnosis of chromosomal imbalance: is less more?

Chromosome analysis is an important component to the diagnosis of congenital anomalies, developmental delay, and mental retardation. Routine chromosome analysis identifies aneuploidy and structural rearrangements greater than 5 Mb but cannot identify abnormalities of the telomeric regions or microdeletions reliably. Molecular cytogenetic techniques were developed to overcome these limitations.