Jay Leonard

Klinefelter's Syndrome (XXY) as a Genetic Model for Psychotic Disorders

Males with an extra‐X chromosome (Klinefelters syndrome) frequently, although not always, have an increased prevalence of psychiatric disturbances that range from attention deficit disorder in childhood to schizophrenia or severe affective disorders during adulthood. In addition, they frequently have characteristic verbal deficits. Thus, examining brain magnetic resonance imaging (MRI) scans of these individuals may yield clues to the influence of X chromosome genes on brain structural variation corresponding to psychiatric and cognitive disorders. Eleven adult XXY and 11 age matched XY male controls were examined with a structured psychiatric interview, battery of cognitive tests, and an MRI scan. Ten of eleven of the XXY men had some form of psychiatric disturbance, four of whom had auditory hallucinations compared with none of the XY controls. Significantly smaller frontal lobe, temporal lobe, and superior temporal gyrus (STG) cortical volumes were observed bilaterally in the XXY men. In addition, diffusion tensor imaging (DTI) of white matter integrity resulted in four regions of reduced fractional anisotropy (FA) in XXY men compared with controls, three in the left hemisphere, and one on the right. These correspond to the left posterior limb of the internal capsule, bilateral anterior cingulate, and left arcuate bundle. Specific cognitive deficits in executive functioning attributable to frontal lobe integrity and verbal comprehension were noted. Thus, excess expression of one or more X chromosome genes influences both gray and white matter development in frontal and temporal lobes, as well as white matter tracts leading to them, and may in this way contribute to the executive and language deficits observed in these adults. Future prospective studies are needed to determine which gene or genes are involved and whether their expression could be modified with appropriate treatments early in life. Brain expressed genes that are known to escape inactivation on extra‐X chromosomes would be prime candidates.

Quality assurance for Duchenne and Becker muscular dystrophy genetic testing: development of a genomic DNA reference material panel.

Duchenne and Becker muscular dystrophies (DMD/BMD) are allelic X-linked recessive disorders that affect approximately 1 in 3500 and 1 in 20,000 male individuals, respectively. Approximately 65% of patients with DMD have deletions, 7% to 10% have duplications, and 25% to 30% have point mutations in one or more of the 79 exons of the dystrophin gene. Most clinical genetics laboratories test for deletions, and some use technologies that can detect smaller mutations and duplications. Reference and quality control materials for DMD/BMD diagnostic and carrier genetic testing are not commercially available. To help address this need, the Centers for Disease Control and Prevention-based Genetic Testing Reference Material Coordination Program, in collaboration with members of the genetic testing and the DMD/BMD patient communities and the Coriell Cell Repositories, have characterized new and existing cell lines to create a comprehensive DMD/BMD reference material panel. Samples from 31 Coriell DMD cell lines from male probands and female carriers were analyzed using the Affymetrix SNP Array 6.0 and Multiplex Ligation-Dependent Probe Amplification (MRC-Holland BV, Amsterdam, the Netherlands), a multiplex PCR assay, and DNA sequence analysis. Identified were 16 cell lines with deletions, 9 with duplications, and 4 with point mutations distributed throughout the dystrophin gene. There were no discordant results within assay limitations. These samples are publicly available from Coriell Institute for Medical Research (Camden, NJ) and can be used for quality assurance, proficiency testing, test development, and research, and should help improve the accuracy of DMD testing.

Delineation of the breakpoints of pure duplication 3q due to a de novo duplication event using SOMA

Delineation of the Breakpoints of Pure Duplication 3q Due to a De Novo Duplication Event Using SOMA A.L. Shanske,* J. Leonard, O. Nahum, D.L. Coppock, and B. Levy Center for Craniofacial Disorders, Children’s Hospital at Montefiore, Albert Einstein College of Medicine, Bronx, New York Coriell Institute for Medical Research, Camden, New York Department of Pathology, Columbia University College of Physicians & Surgeons, New York, New York

Wolf-Hirschhorn Syndrome and Ectrodactyly: New Findings and a Review of the Literature

Wolf–Hirschhorn Syndrome and Ectrodactyly: New Findings and a Review of the Literature Alan L. Shanske,* Naomi Yachelevich, Leena Ala-Kokko, Jay Leonard, and Brynn Levy The Center for Craniofacial Disorders, Children’s Hospital at Montefiore, Albert Einstein College of Medicine, Bronx, New York Connective Tissue Gene Tests, Allentown, Pennsylvania Coriell Institute for Medical Research, Camden, New Jersey Department of Pathology, College of Physicians & Surgeons, Columbia University, New York, New York

Brief Communication: Regional Mapping Panels for Human Chromosomes 1, 2, and 7

The NIGMS Human Genetic Cell Repository has assembled regional mapping panels for human chromosomes 1, 2, and 7 from human rodent somatic cell hybrids submitted to the collection by researchers from 14 different laboratories. All hybrids were characterized initially by the submitters and verified by the Repository. Each hybrid carries a stable defined human segment as a derivative or deletion chromosome. These panels define 8–10 intervals for each chromosome. The panel for chromosome 2 is a new resource. The panels for chromosomes 1 and 7 complement previously published panels. The Repository distributes these regional mapping panels as cell cultures or as DNA. Information about these panels as well as for panels for chromosomes 3, 4, 5, 6, 8, 9, 10, 11, 12, 13, 15, 16, 17, 18, 21, 22, and X may be viewed in the NIGMS Repository electronic catalog (http://locus.umdnj.edu/ptnigms).