Perceived value of trauma autopsy among trauma medical directors and coroners.

Introduction: Although autopsy is acknowledged as essential for improving quality of medical care of trauma patients and accuracy of injury surveillance systems, the autopsy rate has remained well below 100% for certain categories of trauma. We obtained recent documentation of the frequency of autopsy among trauma-related deaths in Ohio, and surveyed coroners and trauma program medical directors (TMDs) about the perceived benefits and challenges of performing autopsy.

Materials And Methods: Copies of death certificates were obtained for the years 1996-2001.

Consistent chromosome abnormalities identify novel polymicrogyria loci in 1p36.3, 2p16.1-p23.1, 4q21.21-q22.1, 6q26-q27, and 21q2.

Polymicrogyria is a malformation of cortical development characterized by loss of the normal gyral pattern, which is replaced by many small and infolded gyri separated by shallow, partly fused sulci, and loss of middle cortical layers. The pathogenesis is unknown, yet emerging data supports the existence of several loci in the human genome. We report on the clinical and brain imaging features, and results of cytogenetic and molecular genetic studies in 29 patients with polymicrogyria associated with structural chromosome rearrangements.

Monosomy 1p36 uncovers a role for OX40 in survival of activated CD4+ T cells.

Monosomy 1p36 is a subtelomeric deletion syndrome associated with congenital anomalies presumably due to haploinsufficiency of multiple genes. Although immunodeficiency has not been reported, genes encoding costimulatory molecules of the TNF receptor superfamily (TNFRSF) are within 1p36 and may be affected. In one patient with monosomy 1p36, comparative genome hybridization and fluorescence in- situ hybridization confirmed that TNFRSF member OX40 was included within the subtelomeric deletion.

Expanding the clinical phenotype of the 3q29 microdeletion syndrome and characterization of the reciprocal microduplication.

Background: Interstitial deletions of 3q29 have been recently described as a microdeletion syndrome mediated by nonallelic homologous recombination between low-copy repeats resulting in an ~1.6 Mb common-sized deletion. Given the molecular mechanism causing the deletion, the reciprocal duplication is anticipated to occur with equal frequency, although only one family with this duplication has been reported.

Diagnosis of microdeletion syndromes by fluorescence in situ hybridization (FISH).

This unit opens with an overview of microdeletions and methods for their detection. It goes on to describe a vast array of autosomal microdeletion syndromes, X-linked microdeletion syndromes, and microduplication syndromes. The final portion of the unit offers guidance for detecting such syndromes with Fluorescence in situ Hybridization (FISH).

Prenatal diagnosis using array CGH.

Microarray-based comparative genomic hybridization (array CGH) is a fast and high-resolution approach to the diagnosis of a large number of genetic syndromes associated with loss or gain of the human genome. This technology has proven to be useful in several clinical settings, including postnatal diagnosis of mental retardation, developmental delay, and congenital malformation syndromes. We describe the use of array CGH for prenatal diagnosis of a range of chromosomal syndromes associated with congenital malformations visible by ultrasound.

Array comparative genomic hybridization in global developmental delay.

Objective: Array-based comparative genomic hybridization (array CGH) is an emerging technology that allows for the genome-wide detection of DNA copy number changes (CNC) such as deletions or duplications. In this study, array-based CGH was applied to a consecutive series of children with previously undiagnosed non-syndromal global developmental delay (GDD) to assess potential etiologic yield.

Methods: The children in this study were drawn from a previously reported consecutive series of children with well-defined GDD.

Neuroimaging findings in children with rare or novel de novo chromosomal anomalies.

Background: De novo constitutional chromosomal anomalies provide important insights into the genetic loci responsible for congenital neurological disorders. However, most phenotypic descriptions of patients with rare chromosomal abnormalities are published as individual case reports or small group studies, making genotype-phenotype correlations unclear. Moreover, many clinical genetic reports do not include neuroimaging.

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.

Genomic analysis of the chromosome 15q11-q13 Prader-Willi syndrome region and characterization of transcripts for GOLGA8E and WHCD1L1 from the proximal breakpoint region.

Background: Prader-Willi syndrome (PWS) is a neurobehavioral disorder characterized by neonatal hypotonia, childhood obesity, dysmorphic features, hypogonadism, mental retardation, and behavioral problems. Although PWS is most often caused by a paternal interstitial deletion of a 6-Mb region of chromosome 15q11-q13, the identity of the exact protein coding or noncoding RNAs whose deficiency produces the PWS phenotype is uncertain. There are also reports describing a PWS-like phenotype in a subset of patients with full mutations in the FMR1 (fragile X mental retardation 1) gene.

Characterization of complex chromosome aberrations in a recurrent meningioma combining standard cytogenetic and array comparative genomic hybridization techniques.

Meningiomas were among the first solid tumors recognized as having cytogenetic alterations. The most consistent changes reported in grade I meningiomas were monosomy 22 or partial 22q deletion. The vast majority of meningiomas are histologically benign, but the prognosis is determined by risk of recurrence after surgical treatment.

Randomized trial comparing 3 methods of postoperative analgesia in gynecology patients: patient-controlled intravenous, scheduled intravenous, and scheduled subcutaneous.

Objective: The objective of the study was to determine whether any of 3 routes of opioid administration (patient-controlled analgesia [PCA], scheduled intermittent intravenous [i.v.], or scheduled intermittent subcutaneous [s.

Monosomy 1p36 deletion syndrome.

Monosomy 1p36 results from a heterozygous deletion of the most distal chromosomal band on the short arm of chromosome 1. Occurring in approximately 1 in 5,000 live births, monosomy 1p36 is the most common terminal deletion observed in humans. Monosomy 1p36 is associated with mental retardation, developmental delay, hearing impairment, seizures, growth impairment, hypotonia, and heart defects.

The identification of microdeletion syndromes and other chromosome abnormalities: cytogenetic methods of the past, new technologies for the future.

Chromosome analysis is an important diagnostic tool in the identification of causes of mental retardation, developmental delay, and other developmental disabilities. Cytogenetic approaches have revealed the chromosomal basis of a large number of genetic syndromes. The recent use of microarray-based comparative genomic hybridization (array CGH) has accelerated the identification of novel cytogenetic abnormalities.

The discovery of microdeletion syndromes in the post-genomic era: review of the methodology and characterization of a new 1q41q42 microdeletion syndrome.

Purpose: The advent of molecular cytogenetic technologies has altered the means by which new microdeletion syndromes are identified. Whereas the cytogenetic basis of microdeletion syndromes has traditionally depended on the serendipitous ascertainment of a patient with established clinical features and a chromosomal rearrangement visible by G-banding, comparative genomic hybridization using microarrays has enabled the identification of novel, recurrent imbalances in patients with mental retardation and apparently nonspecific features. Compared with the "phenotype-first" approach of traditional cytogenetics, array-based comparative genomic hybridization has enabled the detection of novel genomic disorders using a "genotype-first" approach.

Discovery of a previously unrecognized microdeletion syndrome of 16p11.2-p12.2.

We have identified a recurrent de novo pericentromeric deletion in 16p11.2-p12.2 in four individuals with developmental disabilities by microarray-based comparative genomic hybridization analysis.

The clinical utility of enhanced subtelomeric coverage in array CGH.

Telomeric chromosome abnormalities are a substantial cause of mental retardation and birth defects. Although subtelomeric fluorescence in situ hybridization (FISH) probes have been widely used to identify submicroscopic telomeric rearrangements, array-based comparative genomic hybridization (array CGH) has emerged as a more efficient and comprehensive detection method. Due to the clinical relevance of telomeric abnormalities, it has been proposed that array CGH using panels of BAC clones that map to regularly spaced intervals along the length of each telomere could be used to characterize subtelomeric aberrations more precisely in a single experiment.

Fluorochrome-linked immunoassay for functional analysis of the mannose binding lectin complement pathway to the level of C3 cleavage.

The humoral response to invading pathogens is mediated by a repertoire of innate immune molecules and receptors able to recognize pathogen-associated molecular patterns. Mannose binding lectin (MBL) and ficolins are initiation molecules of the lectin complement pathway (LCP) that bridge innate and adaptive immunity. Activation of the MBL-dependent lectin pathway, to the level of C3 cleavage, requires functional MASP-2, C2, C4 and C3, all of which have been identified with genetic polymorphisms that can affect protein concentration and function.

Role of the alternative pathway in the early complement activation following major trauma.

Complement activation has been reported after major trauma. However, little is known about the clinical relevance and the mechanisms of complement activation early after trauma. Therefore, the aim of this study was to measure complement activation, to identify the roles of injury severity and hypoperfusion, to determine the predominant activated pathway, and to identify the clinical significance of early complement activation in trauma patients.

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.

Molecular cytogenetic and rapid aneuploidy detection methods in prenatal diagnosis.

Cytogenetic analysis is an important component of prenatal diagnosis. The ability to rapidly detect aneuploidy and identify small structural abnormalities of fetal chromosomes has been greatly enhanced by the use of molecular cytogenetic technologies. In this review, we will present some of the molecular cytogenetic techniques available to the clinical cytogenetics laboratory.