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Record 1Comparative mapping of the region of human chromosome 7 deleted in williams syndrome. DeSilva U; Massa H; Trask BJ; Green ED Genome Technology Branch, National Human Genome Research Institute, National Institutes of Health, Bethesda, Maryland 20892, USA. Genome Res (UNITED STATES) May 1999, 9 (5) p428-36, ISSN 1088-9051 Languages: ENGLISH Document type: JOURNAL ARTICLE
Williams syndrome (WS) is a complex developmental disorder resulting from the deletion of a large (approximately 1.5-2 Mb) segment of human chromosome 7q11.23. Physical mapping studies have revealed that this deleted region, which contains a number of known genes, is flanked by several large, nearly identical blocks of DNA. The presence of such highly related DNA segments in close physical proximity to one another has hampered efforts to elucidate the precise long-range organization of this segment of chromosome 7. To gain insight about the structure and evolutionary origins of this important and complex genomic region, we have constructed a fully contiguous bacterial artificial chromosome (BAC) and P1-derived artificial chromosome (PAC) contig map encompassing the corresponding region on mouse chromosome 5. In contrast to the difficulties encountered in constructing a clone-based physical map of the human WS region, the BAC/PAC-based map of the mouse WS region was straightforward to construct, with no evidence of large duplicated segments, such as those encountered in the human WS region. To confirm this difference, representative human and mouse BACs were used as probes for performing fluorescence in situ hybridization (FISH) to metaphase and interphase chromosomes. Human BACs derived from the nonunique portion of the WS region hybridized to multiple, closely spaced regions on human chromosome 7q11.23. In contrast, corresponding mouse BACs hybridized to a single site on mouse chromosome 5. Furthermore, FISH analysis revealed the presence of duplicated segments within the WS region of various nonhuman primates (chimpanzee, gorilla, orangutan, and gibbon). Hybridization was also noted at the genomic locations corresponding to human chromosome 7p22 and 7q22 in human, chimpanzee, and gorilla, but not in the other animal species examined. Together, these results indicate that the WS region is associated with large, duplicated blocks of DNA on human chromosome 7q11.23 as well as the corresponding genomic regions of other nonhuman primates. However, such duplications are not present in the mouse.
Record 2Continuing education in neurometabolic disorders--serine deficiency disorders. de Koning TJ; Poll-The BT; Jaeken J Department of Metabolic Diseases, University Children's Hospital Het Wilhelmina Kinderziekenhuis, Utrecht, The Netherlands. Neuropediatrics (GERMANY) Feb 1999, 30 (1) p1-4, ISSN 0174-304X Languages: ENGLISH Document type: JOURNAL ARTICLE; REVIEW; REVIEW, TUTORIAL
Serine deficiency disorders comprise a new group of inborn errors of serine metabolism. Patients affected with these disorders present with major neurological symptoms including congenital microcephaly, seizures, psychomotor retardation or polyneuropathy. The diagnosis of serine deficiency is based on the detection of low concentrations of the amino acids serine and glycine in fasted plasma and cerebrospinal fluid (CSF). Amino acid analysis of cerebrospinal fluid is preferable over plasma analysis, because the deficiencies are more pronounced in CSF. Because of the interference of amino acids absorbed from the diet, diagnostic procedures have to be performed in the fasted state. Although the disorders are probably rare and not many cases have been reported, recognition of serine deficiency is important, given the fact that the disorders are potentially treatable. The clinical symptoms respond well to amino acid replacement therapy. So far, three serine deficiency disorders have been reported; 3-phosphoglycerate dehydrogenase deficiency, 3-phosphoserine phosphatase deficiency and a still unexplained serine deficiency disorder. In this paper, we will discuss the various serine deficiency disorders, their biochemical abnormalities and the results of amino acid replacement therapy. (14 Refs.)
Record 3[Williams syndrome without cardiovascular abnormalities] Sindrome di Williams in assenza di anomalie cardiovascolari. Cincinnati P; Genuardi M; Rutiloni C Sezione Autonoma di Pediatria, Ospedale E. de Santis, Genzano, Roma. Minerva Pediatr (ITALY) Nov 1998, 50 (11) p467-71, ISSN 0026-4946 Languages: ITALIAN Summary Languages: ENGLISH Document type: JOURNAL ARTICLE English Abstract
In a patient with facial dysmorphic traits, growth deficiency, mental retardation but without cardiovascular anomalies, detection of hemizygosity at the elastin locus by FISH analysis confirmed diagnosis of Williams Syndrome (WS). To date, cardiovascular pathology in WS is thought to be the result of a localized response of inelastic vessels to haemodynamic stress in fetal life. Patients with deletion at the elastin locus and no cardiovascular defects suggest that genetic aspects other than hemizygosity must be investigated, such as transcriptional regulation of the elastin gene expression. Moreover, a complete characterization of the region commonly deleted in 7q11.23 is needed before excluding other genes as responsible for the cardiovascular defects. Clinical investigations are requested for selecting patients with partial phenotype, various degrees of tissue damage and different evolution at follow-up.
Record 4A gene-dosage PCR method for the detection of elastin gene deletions in patients with Williams syndrome. del Rio T; Urban Z; Csiszar K; Boyd CD The Pacific Biomedical Research Center, University of Hawaii, Honolulu 96822, USA. Clin Genet (DENMARK) Aug 1998, 54 (2) p129-35, ISSN 0009-9163 Languages: ENGLISH Document type: JOURNAL ARTICLE
Williams syndrome (WS) is a multisystem developmental disorder associated with microdeletions at 7q11.23 that involve several genes, including the elastin gene. Using genomic DNA from a panel of normal individuals and WS patients with established hemizygosity of the elastin gene locus, we have developed a quantitative polymerase chain reaction (PCR)-based gene-dosage assay that rapidly detects the loss of one allele of the elastin gene. Using this procedure, we also studied a family in which the proband was previously diagnosed with WS and her mother with a balanced 7q translocation [t(7:11)(q34;q13)]. Using DNA isolated from buccal smears obtained from several individuals in this family we were able to establish normal disomy at 7q in all family members except for the proband, in which we established hemizygosity at the elastin gene locus. We were also able to successfully infer normal disomy in an unborn child in this family. The rapid diagnostic procedure described here may have a variety of applications, including fine mapping of deletion breakpoints at 7q11.23 associated with WS.
Record 5LIM-kinase1. Stanyon CA; Bernard O Walter and Eliza Hall Institute of Medical Research, Royal Melbourne Hospital, Parkville, Australia. Int J Biochem Cell Biol (ENGLAND) Mar-Apr 1999, 31 (3-4) p389-94, ISSN 1357-2725 Languages: ENGLISH Document type: JOURNAL ARTICLE; REVIEW; REVIEW LITERATURE
LIM-kinase1 (LIMK1) is a serine-only protein kinase that contains LIM and PDZ protein-protein interaction domains which is highly expressed in neurons. Overexpression of LIMK1 in cultured cells results in accumulation of filamentous (F-) actin. LIMK1 phosphorylates cofilin, an actin depolymerisation factor, which is then unable to bind and depolymerise F-actin. Rac-GTP enhances phosphorylation of LIMK1 and cofilin, which leads to accumulation of F-actin, while Rac-GDP and PMA reduce these effects. LIMK1 is therefore a key component of a signal transduction network that connects extracellular stimuli to changes in cytoskeletal structure. Control of cell morphology and mobility via LIMK1 activity may provide novel approaches to cancer therapy. (16 Refs.)
Record 6Refining behavioral phenotypes: personality-motivation in Williams and Prader-Willi syndromes. Dykens EM; Rosner BA University of California, Los Angeles, USA. Am J Ment Retard (UNITED STATES) Mar 1999, 104 (2) p158-69, ISSN 0895-8017 Languages: ENGLISH Document type: CLINICAL TRIAL; JOURNAL ARTICLE
Despite behavioral differences, individuals with Williams or Prader-Willi syndrome share a proneness to certain personality characteristics. We hypothesized that there are qualitative differences in these shared personality features. Personality-motivation (measured using the Reiss Profiles) was compared for equal numbers of age- and gender-matched individuals with Williams or Prader-Willi syndrome or mental retardation due to nonspecific causes. Each syndrome featured aberrant motivational profiles, and similarities were found across groups in various domains. Significant differences emerged in the specific stimuli that motivated behavior in several Reiss Profile domains. Implications are discussed for the "classic" sociable personality in Williams syndrome and for compulsivity in Prader-Willi syndrome. Recommendations are made for treatment and more refined phenotypic research.
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