New insights into the phenotypes of 6q deletions.

Deletions of chromosome 6q are rare. We report 3 new patients with 6q deletions. Case 1 is a male with an interstitial deletion [del(6)(q13q14.

Human Ah receptor (AHR) gene: localization to 7p15 and suggestive correlation of polymorphism with CYP1A1 inducibility.

The mammalian aromatic hydrocarbon receptor (AHR) is a ubiquitous ligand-activated transcription factor. AHR ligands include 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD; dioxin), benzo[a]pyrene, and polychlorinated and polybrominated biphenyls; the endogenous ligand is not yet known. Following ligand binding, the AHR transcriptionally activates genes encoding drug-metabolizing enzymes important in both the metabolic potentiation of substrates to genotoxic reactive intermediates and ultimate carcinogens, and the detoxification of toxic or carcinogenic drugs and other environmental pollutants.

Ullrich-Turner syndrome and neurofibromatosis-1.

There is a well-known association between neurofibromatosis-1 (NF1) and Noonan syndrome-like manifestations, including short stature, short broad neck, and hypertelorism. These anomalies are thought to be due to variable expression of the NF1 gene. We report on two girls with NF1 who were found to have the Ullrich-Turner syndrome.

Prenatal diagnosis of ring chromosome 6 in a fetus with hydrocephalus.

A patient with ring chromosome 6/monosomy 6 mosaicism is presented. At 25 weeks' gestation, ultrasound examination demonstrated fetal hydrocephalus. Amniocentesis was performed.

Cloning and regional assignment of the human myosin heavy chain 12 (MYH12) gene to chromosome band 15q21.

Sequences encoding 1,235 bp of the human myosin heavy chain 12 (MYH12) gene have been cloned from a human brain cDNA library by PCR amplification. The human sequence is 95.8% identical to the mouse sequence at the amino acid level, indicating that the MYH12 gene has been evolutionarily well conserved.

Hemizygosity at the insulin-like growth factor I receptor (IGF1R) locus and growth failure in the ring chromosome 15 syndrome.

The ring chromosome 15 syndrome is characterized by mild-to-severe growth failure. We evaluated the status of the insulin-like growth factor I receptor (IGF1R) gene, which had previously been assigned to band 15q26 in several patients with de novo ring 15 chromosomes, to investigate a possible correlation between disruption or loss of the IGF1R gene with the severe growth failure phenotype. The presence or absence of the IGF1R gene on the ring 15 chromosomes of five patients was ascertained by in situ hybridization and gene-dosage (Southern) blotting.

Gene for a tissue-specific transcriptional activator (EBF or Olf-1), expressed in early B lymphocytes, adipocytes, and olfactory neurons, is located on human chromosome 5, band q34, and proximal mouse chromosome 11.

Murine B lymphocytes, adipocytes, and olfactory neurons contain a DNA-binding protein that participates in the regulation of genes encoding tissue-specific components of signal transduction. Purification and cloning of this protein, termed early B-cell factor (EBF), from murine B lymphocytes and independent cloning of a protein, termed Olf-1, from olfactory neuronal cells revealed virtual complete amino acid sequence identity between these proteins. As a first step towards identifying a human genetic disorder or mouse mutation for which EBF could be a candidate gene, we have chromosomally mapped the corresponding locus in both species.

Chromosome localizations of genes for five cAMP-specific phosphodiesterases in man and mouse.

Cyclic nucleotides are important second messengers that mediate a number of cellular responses to external signals. Cyclic nucleotide phosphodiesterases play a role in signal transduction by regulating the cellular concentrations of these messengers. Here, we have applied Southern analyses of somatic cell hybrid lines and of recombinant inbred (RI) mouse strains as well as fluorescence chromosomal in situ hybridization (FISH) to chromosomally localize five cAMP-specific nucleotide phosphodiesterase genes in human and mouse.

Structure and localization on the X chromosome of the gene coding for the human filopodial protein moesin (MSN).

Moesin is a member of a recently discovered family of closely related proteins that includes ezrin, radixin, and merlin. It is widely expressed in different tissues and cells and has been localized to filopodia and other membranous protrusions that are important for cell-cell recognition and signaling and cell movement. Here, we have localized the coding gene (MSN) to Xq11.

Autosomal recessive neuromuscular disorder in a transgenic line of mice.

We have generated a line of transgenic mice that when homozygous for the transgene develop a severe, adult-onset neuromuscular disorder. This mutation is likely the result of the insertional inactivation of an endogenous gene by the transgene integration. The mutant mice have a gait abnormality with stiffened and/or splayed hind legs, and adopt a hunched posture with some exhibiting kyphosis of the thoracic spine.

Gene for the alpha-subunit of the human interleukin-3 receptor (IL3RA) localized to the X-Y pseudoautosomal region.

Interleukin-3 (IL3) and granulocyte/macrophage colony-stimulating factor (CSF2) stimulate proliferation and differentiation of various hemopoietic cell types. As is characteristic of the cytokine receptor family, the receptors for these proteins comprise alpha- and beta-subunits. While IL3 and CSF2 receptors each have unique alpha- subunits, they share a common beta-subunit.

cDNA cloning of the two subunits of human CAAX farnesyltransferase and chromosomal mapping of FNTA and FNTB loci and related sequences.

The CAAX farnesyltransferase is a heterodimeric enzyme that attaches a farnesyl group to a single cysteine in several cellular proteins. Substrates include the p21ras proteins, nuclear lamins, and several retinal proteins, all of which end with a "CAAXbox," where C is cysteine, A is an aliphatic amino acid, and X is methionine or serine. Full-length cDNAs for the alpha and beta subunits of the rat farnesyltransferase have been cloned, and both have been shown to be essential for catalytic activity.

Human dystroglycan: skeletal muscle cDNA, genomic structure, origin of tissue specific isoforms and chromosomal localization.

Dystroglycan is a novel laminin binding component of the dystrophin-glycoprotein complex which provides a linkage between the subsarcolemmal cytoskeleton and the extracellular matrix. Here we report the cDNA and genomic structure of human dystroglycan. The human dystroglycan is encoded by a single gene (DAG1) mapped to chromosome 3 band p21.

Structural comparison and chromosomal localization of the human and mouse IL-13 genes.

The genomic structure of the recently described cytokine IL-13 has been determined for both human and mouse genes. The nucleotide sequence of a 4.6-kb DNA segment of the human gene is described.

The Vin-1 gene, identified by provirus insertional mutagenesis, is the cyclin D2.

The Vin-1 gene was initially identified as a gene whose expression is altered by the integration of proviruses in the Vin-1 common site of integration in retrovirus-induced rodent T-cell leukemias. We have now isolated the Vin-1 cDNA. Sequencing of the Vin-1 cDNA and Vin-1 exons revealed that the proviruses are integrated at the 5' end of the Vin-1 gene in an inverse transcriptional orientation.

Genes for the dimerization cofactor of hepatocyte nuclear factor-1 alpha (DCOH) are on human and murine chromosomes 10.

Hepatocyte nuclear factor-1 alpha (HNF-1 alpha; gene symbol, TCF1) forms dimers with itself as well as with HNF-1 beta and regulates the expression of several liver-specific genes. Recently, a dimerization cofactor of hepatocyte nuclear factor-1 alpha, called DCOH, has been identified. Here, we report the chromosomal localization of the genes for this cofactor to chromosomes 10 in both humans and mice by Southern blot analyses of somatic cell hybrids.

Molecular cloning, cDNA sequence, and chromosomal assignment of the human radixin gene and two dispersed pseudogenes.

Radixin is a cytoskeletal protein that may be important in linking actin to the plasma membrane. Recent cloning of the murine and porcine radixin cDNAs revealed a protein highly homologous to ezrin and moesin. We have cloned and sequenced the human radixin cDNA and found the predicted amino acid sequence for the human protein to be nearly identical to those predicted for radixin in the two other species.

A serine/proline-rich protein is fused to HRX in t(4;11) acute leukemias.

Translocations involving chromosome band 11q23 in acute leukemias have recently been shown to involve the HRX gene that codes for a protein with significant similarity to Drosophila trithorax. HRX gene alterations are consistently observed in t(4;11) (q21;q23)-carrying leukemias and cell lines by Southern blot analyses and are accompanied by HRX transcripts of anomalous size on Northern blots. HRX-homologous cDNAs were isolated from a library prepared from t(4;11)-carrying acute leukemia cells.

The CD40 ligand, gp39, is defective in activated T cells from patients with X-linked hyper-IgM syndrome.

The prominent role of the CD40 receptor in B cell responses led us to investigate the role of the gp39-CD40 interaction in a group of primary immunodeficient patients with defective antibody production. Here we report that patients with hyper-IgM syndrome (HIM) have a defective gp39-CD40 interaction. B cells from HIM patients express functional CD40, but their T cells do not bind CD40-Ig.

Serotonin receptor 1c gene assigned to X chromosome in human (band q24) and mouse (bands D-F4).

In the mammalian nervous system, serotonin (5-hydroxytryptamine) binds to distinct cell surface receptor subtypes that are defined by their ligand binding and effector-coupling properties. The 5HT1c receptor is a G-protein coupled receptor that stimulates phospholipase C-catalyzed hydrolysis of phosphatidylinositol bisphosphate, leading to the mobilization of intracellular calcium and to the activation of protein kinase C. By using somatic cell hybrid analysis and FISH, we have mapped the HTR1C locus to the human X chromosome, band q24 and to the mouse X chromosome region D-F4.

Tissue-specific expression and chromosome assignment of genes specifying two isoforms of subunit VIIa of human cytochrome c oxidase.

Subunit VIIa of mammalian cytochrome c oxidase (COX; EC 1.9.3.

Molecular genetics of steroid 5 alpha-reductase 2 deficiency.

Two isozymes of steroid 5 alpha-reductase encoded by separate loci catalyze the conversion of testosterone to dihydrotestosterone. Inherited defects in the type 2 isozyme lead to male pseudohermaphroditism in which affected males have a normal internal urogenital tract but external genitalia resembling those of a female. The 5 alpha-reductase type 2 gene (gene symbol SRD5A2) was cloned and shown to contain five exons and four introns.

Recombination of 4p16 DNA markers in an unusual family with Huntington disease.

The Huntington disease (HD) mutation has been localized to human chromosome 4p16, in a 6-Mb region between the D4S10 locus and the 4p telomere. In a report by Robbins et al., a family was identified in which an affected individual failed to inherit three alleles within the 6-Mb region originating from the parental HD chromosome.

Human cyclin B1 gene (CCNB1) assigned to chromosome 5 (q13-qter).

Cyclins play an important role in cell cycle regulation. At least five classes of cyclins have been identified--A, B, C, D, and E. B cyclins are generally of two types in most organisms--B1 and B2.

Gene for lymphoid enhancer-binding factor 1 (LEF1) mapped to human chromosome 4 (q23-q25) and mouse chromosome 3 near Egf.

LEF-1 is a 54-kDa nuclear protein that is expressed specifically in pre-B and T-cells. It binds to a functionally important site in the T-cell receptor alpha enhancer and contributes to maximal enhancer activity. LEF-1 is a member of a family of regulatory proteins that share homology with the high mobility group protein 1 (HMG1).