Partial trisomy 2p and partial monosomy 2q arising from a paternal intrachromosomal 2q-into-2p between-arm insertion and paracentric inversion: molecular cytogenetic characterization of a four-break rearrangement.

We report on a 26-month-old boy with an interstitial duplication of 2p22.3p22.2 and an interstitial deletion of 2q14.1q21.2. The abnormality was derived from his father having a balanced paracentric inversion and pericentric insertion. The deletion in the child was identified by cytogenetic analysis and characterized in more detail by molecular cytogenetics and array comparative genomic hybridization. The latter revealed a 20-Mb deletion in the long arm and a 5.6-Mb duplication in the short arm of chromosome 2. Fluorescence in situ hybridization in paternal chromosomes characterized an intrachromosomal insertion of 2q14.1q21.2 into 2p23; additionally a paracentric inversion of 2p13p23 was observed. The boy with the unbalanced karyotype suffered from severe psychomotor retardation, thrombophilia due to protein C deficiency, and hypertrophic cardiomyopathy and also had phenotypic abnormalities. Most of these features have previously been described in individuals with interstitial deletion of 2q14.1.

Fine mapping of the human pentraxin gene region on chromosome 1q23.

The 1q21 to 25 region of human chromosome 1 contains genes which encode proteins with immune- and inflammation-associated functions. These include the pentraxin genes, for C-reactive protein (CRP), serum amyloid P (SAP) protein (APCS),a nd a CRP pseudogene (CRPP1). The region of chromosome 1 containing this cluster is syntenic with distal mouse chromosome 1. We constructed an approximately 1.4 megabase yeast artificial chromosome (YAC) contig with the pentraxin genes at its core. This four-YAC contig includes other genes with immune functions including the FCER1A gene, which encodes the alpha-subunit of the IgE high-affinity Fc receptor and the IFI-16 gene, an interferon-gamma-induced gene. In addition, it contains the histone H3F2 and H4F2 genes and the gene for erythroid alpha-spectrin (SPTA1). The gene order is cen.-SPTA1-H4F2-H3F2-IFI-16-CRP-CRPP1-APCS -FCER1A- tel. The contig thus consists of a cluster of genes whose products either have immunological importance, bind DNA, or both.

Characterization of a novel zinc finger gene (ZNF165) mapping to 6p21 that is expressed specifically in testis.

Clone ZF388 was identified during the course of expressed sequence tag analysis of human adult testis cDNAs as being a member of the C2H2 zinc finger gene family. Northern blot analysis of a range of 16 different human tissues has shown that clone ZF388 detects a single 2.2-kb transcript and that the expression of this mRNA species is strictly specific to the testis. Sequence analysis of ZF388 and other clones isolated by rescreening a testis cDNA library has defined a transcript with an extensive N-terminal acidic domain containing 17% aspartic and glutamic acid residues and a C-terminal domain composed of five zinc finger motifs linked through the highly conserved sequence TGE-KPYE. This gene has been designated ZNF165. Analysis of somatic cell hybrids containing single human chromosomes shows that ZNF165 maps to chromosome 6. Fluorescence in situ hybridization of cDNA insert probes to male metaphase spreads shows that the ZNF165 transcript maps to 6p21 close to the human MHC region. Human 6p21 is homologous with the distal inversion of the mouse t-complex, which has been shown to contain a cluster of genes expressed specifically in the testis.

Prenatal detection of trisomy 21 in uncultured amniocytes by fluorescence in situ hybridization: a prospective study.

A prospective study was undertaken to evaluate the use of fluorescence in situ hybridization (FISH) for the detection of trisomy 21 in interphase nuclei of uncultured amniotic fluid cells. Five hundred cases were analysed in situ and classified as normal or abnormal; the results were subsequently checked against the cytogenetic findings. Four hundred and ninety-three were correctly identified as normal with an 86.6 per cent average frequency of scored nuclei exhibiting two signals; six cases were correctly identified as trisomic for chromosome 21 with 81.7 per cent of scored nuclei exhibiting three signals; and one abnormal case involving an unbalanced chromosome 21:21 translocation was falsely scored as normal due to poor hybridization/detection efficiency. The method has been substantially improved and simplified so that it is suitable for the rapid detection of trisomy 21. As aneuploidy detection in interphase does not identify structural chromosome aberrations, it is not a substitute for fetal chromosome analysis.

Rapid prenatal diagnosis of aneuploidy from uncultured amniotic fluid cells using five-colour fluorescence in situ hybridization.

In this paper we describe the use of five-colour fluorescence in situ hybridization for prenatal diagnosis of aneuploidy using uncultured amniotic fluid cells. The analysis is based on ratio mixing of dual-labelled probes and digital imaging for the detection and visualization of five different probes specific for the five target chromosomes, 13, 18, 21, X, and Y. A retrospective blind analysis of 30 coded uncultured amniotic fluid samples correctly detected fetal sex and five trisomy 21 cases. Multicolour fluorescence in situ hybridization used in this way allows rapid and simultaneous detection of the most frequent aneuploidies.