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Record 1Micro-deletion detected by fluorescent in situ hybridization for Williams syndrome. Dewan K; Borgaonkar DS; Bartoshesky LE; Tuttle D Department of Pathology, Christiana Care Health Services, Newark, DE, USA. Del Med J (UNITED STATES) Nov 1999, 71 (11) p467-9, ISSN 0011-7781 Languages: ENGLISH Document type: JOURNAL ARTICLE
Record 2 Elastin region deletions in Williams syndrome. Zhang J; Kumar A; Roux K; Williams CA; Wallace MR Department of Pediatrics, University of Florida College of Medicine, Gainesville 32610-0296, USA. Genet Test (UNITED STATES) 1999, 3 (4) p357-9, ISSN 1090-6576 Languages: ENGLISH Document type: JOURNAL ARTICLEWilliams syndrome (WS) is considered a contiguous gene syndrome, with most patients having a 1.5-Mb deletion of chromosome 7q11.23 containing the elastin gene and flanking genes. Studies of the frequency, extent, and origin of these deletions are ongoing in many labs to discover ultimately the molecular and pathogenetic basis for WS. An analysis of 9 sporadic WS families with typical phenotypes was performed by genotyping polymorphisms in the region. This study revealed deletions in all 9 patients, with one showing a novel deletion extending much further centromeric than any other WS deletions yet reported.
Record 3Proteins of the ADF/cofilin family: essential regulators of actin dynamics. Bamburg JR Department of Biochemistry and Molecular Biology, Colorado State University, Fort Collins 80523, USA. [email protected] Annu Rev Cell Dev Biol (UNITED STATES) 1999, 15 p185-230, ISSN 1081-0706 Languages: ENGLISH Document type: JOURNAL ARTICLE; REVIEW; REVIEW, ACADEMIC
Ubiquitous among eukaryotes, the ADF/cofilins are essential proteins responsible for the high turnover rates of actin filaments in vivo. In vertebrates, ADF and cofilin are products of different genes. Both bind to F-actin cooperatively and induce a twist in the actin filament that results in the loss of the phalloidin-binding site. This conformational change may be responsible for the enhancement of the off rate of subunits at the minus end of ADF/cofilin-decorated filaments and for the weak filament-severing activity. Binding of ADF/cofilin is competitive with tropomyosin. Other regulatory mechanisms in animal cells include binding of phosphoinositides, phosphorylation by LIM kinases on a single serine, and changes in pH. Although vertebrate ADF/cofilins contain a nuclear localization sequence, they are usually concentrated in regions containing dynamic actin pools, such as the leading edge of migrating cells and neuronal growth cones. ADF/cofilins are essential for cytokinesis, phagocytosis, fluid phase endocytosis, and other cellular processes dependent upon actin dynamics. (215 Refs.)
Record 4Configural and local processing of faces in children with Williams syndrome. Deruelle C; Mancini J; Livet MO; Casse-Perrot C; de Schonen S Center of Research in Cognitive Neuroscience, CNRS, Marseille, France. [email protected] Brain Cogn (UNITED STATES) Dec 1999, 41 (3) p276-98, ISSN 0278-2626 Languages: ENGLISH Document type: JOURNAL ARTICLE
Three experiments investigated face processing in children with Williams syndrome (WS). In Experiment 1, the ability to discriminate different aspects of faces was compared between WS subjects and a group of children individually matched for chronological age (CA-matches) and another group matched for mental age (MA-matches). In Experiments 2 and 3, the ability to process the local and configural aspects of geometrical patterns and faces was assessed within the same groups of subjects. The results indicated that the WSs' overall performance on face recognition was below that of the CA-matches, but similar to that of the MA-matches. This study revealed in addition that the CA- and MA-matches showed a bias toward a configural mode of face and geometrical shape processing, whereas children with WS did not show any bias. These findings suggest that face processing undergoes an abnormal developmental course in WS. Copyright 1999 Academic Press.
Record 5A transcription factor involved in skeletal muscle gene expression is deleted in patients with Williams syndrome. Tassabehji M; Carette M; Wilmot C; Donnai D; Read AP; Metcalfe K University Department of Medical Genetics, St Mary's Hospital, Manchester, UK. [email protected] Eur J Hum Genet (ENGLAND) Oct-Nov 1999, 7 (7) p737-47, ISSN 1018-4813 Languages: ENGLISH Document type: JOURNAL ARTICLE
Williams-Beuren syndrome (WS) is a developmental disorder caused by a hemizygous microdeletion of approximately 1.4MB at chromosomal location 7q11.23. The transcription map of the WS critical region is not yet complete. We have isolated and characterised a 3.4 kb gene, GTF3, which occupies about 140 kb of the deleted region. Northern blot analysis showed that the gene is expressed in skeletal muscle and heart, and RT-PCR analysis showed expression in a range of adult tissues with stronger expression in foetal tissues. Part of the conceptual GTF3 protein sequence is almost identical to a recently reported slow muscle-fibre enhancer binding protein MusTRD1, and shows significant homology to the 90 amino-acid putative helix-loop-helix repeat (HLH) domains of the transcription factor TFII-I (encoded for by the gene GTF2I). These genes may be members of a new family of transcription factors containing this HLH-like repeated motif. Both GTF3 and GTF2I map within the WS deleted region, with GTF2I being positioned distal to GTF3. GTF3 is deleted in patients with classic WS, but not in patients we have studied with partial deletions of the WS critical region who have only supravalvular aortic stenosis. A feature of WS is abnormal muscle fatiguability, and we suggest that haploinsufficiency of the GTF3 gene may be the cause of this.
Record 6Second-order belief attribution in Williams syndrome: intact or impaired? Sullivan K; Tager-Flusberg H Eunice Kennedy Shriver Center, Center for Research on Developmental Disorders, Waltham, MA 02452, USA. [email protected] Am J Ment Retard (UNITED STATES) Nov 1999, 104 (6) p523-32, ISSN 0895-8017 Languages: ENGLISH Document type: JOURNAL ARTICLE
Second-order mental state attribution in a group of children with Williams syndrome was investigated. The children were compared to age, IQ, and language-matched groups of children with Prader-Willi syndrome or nonspecific mental retardation. Participants were given two trials of a second-order reasoning task. No significant differences between the Williams syndrome and Prader-Willi or mentally retarded groups on any of the test questions were found. Results contrast with the view that individuals with Williams syndrome have an intact theory of mind and suggest that in their attributions of second-order mental states, children with Williams syndrome perform no better than do other groups of children with mental retardation.
Record 7Surgical treatment of aortic arch hypoplasia in infants and children with biventricular hearts. Poirier NC; Van Arsdell GS; Brindle M; Thyagarajan GK; Coles JG; Black MD ; Freedom RM; Williams WG Division of Cardiovascular Surgery, The Hospital For Sick Children, Toronto, Ontario, Canada. Ann Thorac Surg (UNITED STATES) Dec 1999, 68 (6) p2293-7, ISSN 0003-4975 Languages: ENGLISH Document type: JOURNAL ARTICLE
BACKGROUND: Results of aortic arch reconstruction in the setting of biventricular physiology are well documented in the adult population, however, in children, surgical outcome of this subgroup of patients is less clear. METHODS: We studied the clinical outcomes of 37 children aged 8 days to 15 years (median 26 months), who underwent aortic arch reconstruction for arch hypoplasia from 1982 to 1997. The children were divided into three groups: Group 1 (20 patients) had isolated aortic arch lesions, Group 2 (13 patients) had associated intra-cardiac pathology yet conserving a biventricular physiology, Group 3 (4 patients) had Williams Syndrome. Previous interventions for coarctation had been performed in 30 patients (81%). Arch repair consisted of a patch aortoplasty in the majority of patients (35 of 37 children). RESULTS: Operative mortality occurred in 5 children, 4 in Group 2 (31%), 1 in Group 3 (25%) and none in Group 1. Permanent neurological complications occurred in 2 children (5 %). During the follow-up, which ranged from 1 month to 8 years, balloon angioplasty for arch obstruction was required in 1 child. There was one late death, associated with a subsequent intra-cardiac repair. CONCLUSIONS: Aortic arch surgery in children with isolated arch hypoplasia, is associated with excellent early and late survival in addition to a low reintervention rate. Alternative perfusion and operative strategies must be implemented in infants with associated intra-cardiac anomalies to improve results.
Record 8Cognitive modularity and genetic disorders [see comments] Paterson SJ; Brown JH; Gsodl MK; Johnson MH; Karmiloff-Smith A Neurocognitive Development Unit, Institute of Child Health, University College, London WC1N 1EH, UK. Science (UNITED STATES) Dec 17 1999, 286 (5448) p2355-8, ISSN 0036-8075 Comment in Science 1999 Dec 17;286(5448):2283-4 Languages: ENGLISH Document type: JOURNAL ARTICLE
This study challenges the use of adult neuropsychological models for explaining developmental disorders of genetic origin. When uneven cognitive profiles are found in childhood or adulthood, it is assumed that such phenotypic outcomes characterize infant starting states, and it has been claimed that modules subserving these abilities start out either intact or impaired. Findings from two experiments with infants with Williams syndrome (a phenotype selected to bolster innate modularity claims) indicate a within-syndrome double dissociation: For numerosity judgments, they do well in infancy but poorly in adulthood, whereas for language, they perform poorly in infancy but well in adulthood. The theoretical and clinical implications of these results could lead to a shift in focus for studies of genetic disorders.
Record 9Perspectives: cognition. An innate basis for language? [comment] Bishop DV Department of Experimental Psychology, University of Oxford, Oxford OX1 3UD, UK. [email protected] Science (UNITED STATES) Dec 17 1999, 286 (5448) p2283-4, ISSN 0036-8075 Comment on Science 1999 Dec 17;286(5448):2355-8 Languages: ENGLISH Document type: COMMENT; JOURNAL ARTICLE
Record 10A case of Williams syndrome with a large, visible cytogenetic deletion [letter] Wu YQ; Nickerson E; Shaffer LG; Keppler-Noreuil K; Muilenburg A J Med Genet (ENGLAND) Dec 1999, 36 (12) p928-32, ISSN 0022-2593 Languages: ENGLISH Document type: LETTER
Record 11Deficient coacervation of two forms of human tropoelastin associated with supravalvular aortic stenosis. Wu WJ; Weiss AS Department of Biochemistry, University of Sydney, NSW, Australia. Eur J Biochem (GERMANY) Nov 1999, 266 (1) p308-14, ISSN 0014-2956 Languages: ENGLISH Document type: JOURNAL ARTICLE
Human tropoelastin associates by coacervation and is subsequently cross-linked to make elastin. In Williams syndrome, defective elastin deposition is associated with hemizygous deletion of the tropoelastin gene in supravalvular aortic stenosis (SVAS). Remarkably, point-mutation forms of SVAS correspond to incomplete forms of tropoelastin which include in-frame termination by nonsense mutations, yet the resulting phenotype of these disorders is not explained because expression variably occurs from both normal and mutant alleles. Proteins corresponding to two truncated tropoelastin mutants were expressed and purified to homogeneity. Coacervation of these proteins occurred as expected with increasing temperature, but substantially contrasted with that of the performance of a normal tropoelastin. Significantly, association by coacervation of the truncated SVAS tropoelastin molecules was negligible at 37 degrees C, which contrasted with the substantial coacervation seen for normal tropoelastin. Furthermore their midpoints of coacervation increased and correlated with the extent of deletion, in accord with the loss of hydrophobic regions required for tropoelastin association. Their secondary structures are similar, as evidenced by CD studies. We propose a model for point-mutation SVAS in which aberrant tropoelastin molecules are incompetent and are mainly excluded from participation in coacervation and consequently in elastogenesis. These forms of SVAS may consequently be considered functionally similar to a hemizygous deletion, and mark point-mutation SVAS as a disorder of defective coacervation.
Record 12[Fluorescence in situ hybridization in the study of chromosomal abnormalities] Fluorescentie-in-situhybridisatie bij het onderzoek naar chromosomale afwijkingen. Hoovers JM; Mellink CH; Leschot NJ Academisch Medisch Centrum, afd. Klinische Genetica, Amsterdam. Ned Tijdschr Geneeskd (NETHERLANDS) Nov 6 1999, 143 (45) p2265-8, ISSN 0028-2162 Languages: DUTCH Summary Languages: ENGLISH Document type: JOURNAL ARTICLE; REVIEW; REVIEW, TUTORIAL English Abstract
Classical cytogenetics has a low resolving power and allows analysis of dividing cells only. In fluorescence in situ hybridization (FISH), a DNA fragment is stained with a fluorescent marker, after which this fragment is brought into contact with a patient's DNA. The stained fragment can bind to a corresponding fragment, revealing its presence or absence. Using FISH, every desired DNA sequence (from a whole chromosome to one gene) can be stained. In this way it is also possible to diagnose microdeletion syndromes, such as the Williams syndrome, the DiGeorge syndrome and submicroscopic chromosome anomalies that play a part in mental handicaps. FISH also allows analysis of non-dividing cells. In this way it is possible for instance rapidly to examine uncultured amniotic fluid cells for the commoner trisomies or to find foetal erythrocytes in a pregnant woman's blood. It is also possible to demonstrate tumour-specific breaking points. By application of FISH to microarrays it is possible to study a large number of genes simultaneously for the presence of a particular number of DNA sequences linked to a clinical abnormality. (13 Refs.)
Record 13Identification of GTF2IRD1, a putative transcription factor within the Williams-Beuren syndrome deletion at 7q11.23. Franke Y; Peoples RJ; Francke U Department of Genetics, Stanford University School of Medicine, Stanford CA, USA. [email protected] Cytogenet Cell Genet (SWITZERLAND) 1999, 86 (3-4) p296-304, ISSN 0301-0171 Languages: ENGLISH Document type: JOURNAL ARTICLE
Williams-Beuren syndrome (WBS) is a microdeletion syndrome caused by haploinsufficiency of genes at 7q11.23. Here we describe the identification and characterization of a novel gene named GTF2IRD1, for GTF2I-repeat domain 1, within the WBS deletion region. Northern blot analysis revealed ubiquitous expression during development with two transcripts of 3.6 kb and 5.0 kb generated by alternative splicing. GTF2IRD1 encodes a protein of 944 amino acids that contains a region of high similarity to a unique motif with helix-loop-helix forming potential occurring within the transcription factor GTF2I. Analogous to TFII-I, the product of GTF2IRD1 may have the ability to interact with other HLH-proteins and function as a transcription factor or as a negative transcriptional regulator. A recent report of the identification of a muscle-specific transcription factor, MusTRD1, supports this hypothesis (O'Mahoney et al., 1998). The open reading frame described for MusTRD1 is identical to that of GTF2IRD1; however, the putative MusTRD1-protein is 486 amino acids shorter than the predicted protein encoded by GTF2IRD1. A heterozygous deletion of GTF2IRD1 may contribute to the complex WBS phenotype.
Record 14TBL2, a novel transducin family member in the WBS deletion: characterization of the complete sequence, genomic structure, transcriptional variants and the mouse ortholog. Perez Jurado LA; Wang YK; Francke U; Cruces J Servicio de Genetica, Hospital Universitario La Paz, Madrid, Spain. [email protected] Cytogenet Cell Genet (SWITZERLAND) 1999, 86 (3-4) p277-84, ISSN 0301-0171 Languages: ENGLISH Document type: JOURNAL ARTICLE
Williams-Beuren syndrome (WBS) is a developmental disorder with multi-system manifestations caused by haploinsufficiency for contiguous genes deleted in chromosome region 7q11.23. The size of the deletion is similar in most patients due to a genomic duplication that predisposes to unequal meiotic crossover events. While hemizygosity at the elastin locus is responsible for the cardiovascular features, the contribution of other genes to the WBS phenotype remains to be demonstrated. We have identified a novel gene, TBL2, in the common WBS deletion. TBL2 is expressed as a 2. 4-kb transcript predominantly in testis, skeletal muscle, heart and some endocrine tissues, with a larger approximately 5-kb transcript detected ubiquitously at lower levels. TBL2 encodes a protein with four putative WD40-repeats. An alternatively spliced transcript in TBL2 introduces a novel second exon with an in frame stop codon. This mRNA encodes a 75 amino acid protein with 43 amino acids identical to TBL2 at the N-terminus and no known functional domain. The mouse homolog, Tbl2, shows 84% sequence identity at the nucleotide level and 92% similarity at the amino acid level. Comparison of the mouse and human sequences identifies a conserved region that extends upstream of the previously published sequence with an initiation codon common to both species that adds 21 amino acids at the N-terminus. The Tbl2 gene has been mapped to mouse chromosome 5 in a region of conserved synteny with human 7q11.23. Since haploinsufficiency has been shown for other WD-repeat containing proteins, hemizygosity of TBL2 may contribute to some of the aspects of the complex WBS phenotype.
Record 15Early development (5 to 48 months) in Williams syndrome. A study of 14 children [see comments] Plissart L; Fryns JP Centre for Human Genetics, University Hospital of Leuven, Belgium. Genet Couns (SWITZERLAND) 1999, 10 (2) p151-6, ISSN 1015-8146 Comment in Genet Couns 1999 ;10(2):195-6 Languages: ENGLISH Document type: JOURNAL ARTICLE
At what age do children with Williams syndrome (WS) achieve major developmental milestones? Is their early development harmonious or are some of the typical discrepancies described in older children already noticeable? To address these questions we analysed information gathered over a five year period on 14 children with WS. Each child was evaluated at least twice between the ages of 5 and 48 months, using the Bayley Scales of Infant Development and during more informal observation sessions. Parents and professionals were also interviewed. This analysis provided us with an outline for "developmental norms" for children with WS and allowed us to conclude that, even before the age of 4 years, children with WS display a typical profile in their abilities. Expressive language skills are less delayed in contrast to the important delay in language comprehension and fine motor skills.
Record 16Early development of children with Williams syndrome. Sarimski K Kinderzentrum Munchen, Germany. Genet Couns (SWITZERLAND) 1999, 10 (2) p141-50, ISSN 1015-8146 Languages: ENGLISH Document type: JOURNAL ARTICLE
Developmental observations in ten young children with Williams syndrome (1-6 years old) are presented from developmental tests, symbolic play sessions and play sessions with a special educator following the non-directive Montessori approach. There is a considerable individual variability in performance. Overall, the children are engaged in goal-directed activities for more than 35% of the time during play sessions. Overactivity and distractability seem to be more age-dependent and situation-specific than thought before. Developmental interventions may include play sessions following the Montessori approach.
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