Institutional profile: translational pharmacogenomics at the Icahn School of Medicine at Mount Sinai.

For almost 50 years, the Icahn School of Medicine at Mount Sinai has continually invested in genetics and genomics, facilitating a healthy ecosystem that provides widespread support for the ongoing programs in translational pharmacogenomics. These programs can be broadly cataloged into discovery, education, clinical implementation and testing, which are collaboratively accomplished by multiple departments, institutes, laboratories, companies and colleagues. Focus areas have included drug response association studies and allele discovery, multiethnic pharmacogenomics, personalized genotyping and survey-based education programs, pre-emptive clinical testing implementation and novel assay development.

A Conversation with Kurt and Rochelle Hirschhorn.

In this interview, Kurt and Rochelle Hirschhorn talk with their son, Joel, about their research and collaborations, the early years of medical genetics, the development of genetic counseling, the challenges of being a woman in science, and new challenges and directions for the study of human genetics.

Tetrasomy 15q26: a distinct syndrome or Shprintzen-Goldberg syndrome phenocopy?

Purpose: The aim of this study was to characterize the clinical phenotype of patients with tetrasomy of the distal 15q chromosome in the form of a neocentric marker chromosome and to evaluate whether the phenotype represents a new clinical syndrome or is a phenocopy of Shprintzen-Goldberg syndrome.

Methods: We carried out comprehensive clinical evaluation of four patients who were identified with a supernumerary marker chromosome. The marker chromosome was characterized by G-banding, fluorescence in situ hybridization, single nucleotide polymorphism oligonucleotide microarray analysis, and immunofluorescence with antibodies to centromere protein C.

Chronic kidney disease and GWAS: "the proper study of mankind is man".

Genome-wide association studies (GWAS) have been applied to complex diseases such as diabetes and hypertension, successfully uncovering strong gene associations of potential pathophysiologic significance. Recently, two studies (Köttgen et al., 2010; Chambers et al.

Clinical utility of array CGH for the detection of chromosomal imbalances associated with mental retardation and multiple congenital anomalies.

Microarray-based comparative genomic hybridization (array CGH) has revolutionized clinical cytogenetics, as it provides a relatively quick method to scan the genome for gains and losses of chromosomal material with significantly higher resolution and greater clinical yield than was previously possible. A number of different array CGH platforms have emerged and are being used successfully in the diagnostic setting. In the past few years, these new methodologies have led to the identification of novel genomic disorders in patients with developmental delay/mental retardation and/or multiple congenital anomalies (DD/MR/MCA) as well as the discovery that each individual carries inherited copy number variations (CNV) whose contributions to genetic variation and complex disease are not yet well understood.

A short history of the initial discovery of the Wolf-Hirschhorn syndrome.

Deletion of the short arm of chromosome 4 (4p-) was first described in 1961 [Hirschhorn and Cooper, 1961], and the second case of 4p- was published in 1965 [Hirschhorn et al., 1965]. This short history describes the original case and the sequence of events leading to the publications.

Multiple hemangiomas in a patient with a t(3q;4p) translocation: an infrequent association with Wolf-Hirschhorn syndrome.

We report on the clinical phenotype of an infant with a duplication of the terminal portion of the long arm of chromosome 3(q26.3-qter) and a deletion of the terminal portion of the short arm of chromosome 4(p16.3) with multiple hemangiomas and a hamartoma.

Incidence and spectrum of chromosome abnormalities in spontaneous abortions: new insights from a 12-year study.

Purpose: Despite advances in harvesting and culturing techniques, analysis of the impact of these improvements on the observed frequency of chromosomal abnormalities in spontaneous abortions (SAB) has not been determined. We sought to evaluate the effect of these refinements on the success rate of our cultures and on the resulting frequency of detected chromosomal abnormalities.

Methods: Between 1990 and 2002, 2301 specimens obtained from the products of conception (POC) of SABs were submitted to our laboratory for cytogenetic analysis.

The etiology of Wolf-Hirschhorn syndrome.

Wolf-Hirschhorn syndrome (WHS) is defined by a collection of core characteristics, which include mental retardation, epilepsy, growth delay and cranio-facial dysgenesis. The disorder is caused by sub-telomeric deletions in the short arm of chromosome 4. The severity of the core characteristics is highly variable, and additional problems, including midline fusion defects, occur at lower frequency.

Pesticide testing in humans: ethics and public policy.

Pesticide manufacturers have tested pesticides increasingly in human volunteers over the past decade. The apparent goal of these human studies is to establish threshold levels for symptoms, termed "no observed effect levels." Data from these studies have been submitted to the U.

A history of medical genetics in pediatrics.

Medical genetics emerged from a basic science only one half century ago. Scientists and physicians housed in a variety of basic science and clinical departments have accomplished many of the major advances in the study of genetic diseases in children. A scientific approach to human genetics emerged in 1948 with the establishment of the American Society of Human Genetics.

First clinical application of comparative genomic hybridization and polar body testing for preimplantation genetic diagnosis of aneuploidy.

Objective: To develop a preimplantation genetic diagnosis (PGD) protocol that allows any form of chromosome imbalance to be detected.

Design: Case report employing a method based on whole-genome amplification and comparative genomic hybridization (CGH).

Setting: Clinical IVF laboratory.

Chromosome 13q neocentromeres: molecular cytogenetic characterization of three additional cases and clinical spectrum.

We report three new cases of chromosome 13 derived marker chromosomes, found in unrelated patients with dysmorphisms and/or developmental delay. Molecular cytogenetic analysis was performed using fluorescence in situ hybridization (FISH) with chromosome-specific painting probes, alpha satellite probes, and physically mapped probes from chromosome 13q, as well as comparative genomic hybridization (CGH). This analysis demonstrated that these markers consisted of inversion duplications of distal portions of chromosome 13q that have separated from the endogenous chromosome 13 centromere and contain no detectable alpha satellite DNA.

Unique case of mosaicism involving two morphologically similar marker chromosomes of different centric origin in a patient with developmental delay.

A five-year-old Caucasian male presented with developmental delay, minor dysmorphic features, and hyperactivity. Cytogenetic analysis showed the presence of a marker chromosome in the majority of cells analyzed. Fluorescence in situ hybridization (FISH) analyses using several alpha satellite probes, including D13Z1/D21Z1, did not reveal any signal on the marker chromosome.

Delineation of the dup5q phenotype by molecular cytogenetic analysis in a patient with dup5q/del 5p (cri du chat).

An infant girl presented with multiple congenital abnormalities and a distinctive mewing cry. Her karyotype was 46,XX,add5p. Chromosome analysis on the mother revealed an apparently balanced pericentric inversion of chromosome 5, with the precise position of the breakpoints not clearly discernable by GTG banding, 46,XX,inv(5)(p15.

A comprehensive review of genetic association studies.

Most common diseases are complex genetic traits, with multiple genetic and environmental components contributing to susceptibility. It has been proposed that common genetic variants, including single nucleotide polymorphisms (SNPs), influence susceptibility to common disease. This proposal has begun to be tested in numerous studies of association between genetic variation at these common DNA polymorphisms and variation in disease susceptibility.