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Record 1Refinement of the genomic structure of STX1A and mutation analysis in nondeletion Williams syndrome patients. Wu Yuan-Qing; Bejjani Bassem A; Tsui Lap-Chee; Mandel Ariane; Osborne Lucy R; Shaffer Lisa G Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, Texas 77030, USA. American journal of medical genetics (United States) Apr 22 2002, 109 (2) p121-4, ISSN 0148-7299 Document type: Journal Article Languages: ENGLISH Main Citation Owner: NLM Record type: Completed
Williams syndrome (WS) is a contiguous gene deletion disorder in which the commonly deleted region contains at least 17 genes. One of these genes, Syntaxin 1A (STX1A), codes for a protein that is highly expressed in the nervous system and is essential for the docking of synaptic vesicles with the presynaptic plasma membrane. In this study, we refine the complete genomic structure of the human STX1A gene by direct sequencing and primer walking of bacterial artificial chromosome (BAC) clones and show that STX1A contains at least 10 exons and 9 introns. The length of exons range from 27 bp to 138 bp and all splice sites conform to the GT-AG rule. Investigation of the STX1A gene sequence in five WS patients without detectable deletions did not identify any point mutations. Although the regulatory elements that control STX1A transcription were not examined, these results do not support a role for STX1A in the WS phenotype. Copyright 2002 Wiley-Liss, Inc. Record Date Created: 20020523
Record 2[In Process Citation] Sindrome de Williams: estudio clinico, citogenetico, neurofisiologico y neuroanatomico. Aravena Teresa; Castillo Silvia; Carrasco Ximena; Mena Ismael; Lopez Javier; Rojas Juan P; Rosemberg Carol; Schroter Carolina; Aboitiz Francisco Seccion de Genetica, Hospital Clinico de la Universidad de Chile, Santos Dumont 999, 5o piso sector B. Independencia, Santiago, Chile. [email protected] Revista medica de Chile (Chile) Jun 2002, 130 (6) p631-7, ISSN 0034-9887 Document type: Journal Article Languages: SPANISH Main Citation Owner: NLM Record type: In Process
BACKGROUND: Williams syndrome (WS) is a genetically based disorder caused by deletion of elastin and contiguous genes on chromosome 7q11.23. This syndrome is characterized by multiorganic involvement with dysmorphic facial features and a distinctive cognitive profile. It is an interesting model for elucidation of relationships between brain, cognition and genes. Patients have a visual-spatial cognition impaired with relative strengths in social and language abilities. AIM: To report clinical, cytogenetic, neurophysiological and neuroanatomic features in 44 patients referred as WS. PATIENTS AND METHODS: Forty four patients, aged 2 to 17 years, with the clinical diagnosis of Williams syndrome were studied with fluorescence in situ hybridization (FISH). In three cases, electrophysiological and neuroimaging studies were performed. RESULT: The deletion was confirmed in 23 patients. In three patients with neurophysiological studies, event related potentials suggested a cognitive difficulty in detecting and processing visual stimuli. Magnetic resonance imaging showed normal brain morphology. SPECT showed hypoperfusion of the right frontal lobe and bilateral anterior cingulum hyperperfusion. CONCLUSIONS: There are functional alterations in the brains of patients with Williams, which may be related to the cognitive deficits. Record Date Created: 20020826
Record 3A study of relative clauses in Williams syndrome. Grant Julia; Valian Virginia; Karmiloff-Smith Annette Neurocognitive Development Unit, Institute of Child Health, 30 Guilford Street, London, WC1N 1EH, UK. Journal of child language (England) May 2002, 29 (2) p403-16, ISSN 0305-0009 Document type: Journal Article Languages: ENGLISH Main Citation Owner: NLM Record type: Completed
Despite growing empirical evidence to the contrary, claims continue to be made that the grammar of people with Williams syndrome (WS) is intact. We show that even in a simple elicited imitation task examining the syntax of relative clauses, older children and adults with WS (n = 14, mean age = 17;0 years) only reach the level of typical five-year-old controls. When tested systematically in a number of different laboratories, all aspects of WS language show delay and/or deviance throughout development. We conclude that the grammatical abilities of people with WS should be described in terms of relative rather than absolute proficiency, and that the syndrome should no longer be used to bolster claims about the existence of independently functioning, innately specified modules in the human brain. Record Date Created: 20020711
Record 4[Intractable infective endocarditis associated with supraaortic stenosis in Williams syndrome: a case report] Maruyoshi Hidetomo; Nakatani Satoshi; Yasumura Yoshio; Nakajima Hiroyuki; Niwaya Kazuo; Sasako Yoshikado; Ando Motomi; Miyatake Kunio; Yamagishi Masakazu Divisions of Cardiology, National Cardiovascular Center, Osaka. Journal of cardiology (Japan) Jul 2002, 40 (1) p25-30, ISSN 0914-5087 Document type: Journal Article ; English Abstract Languages: JAPANESE Main Citation Owner: NLM Record type: Completed
A 17-year-old man with supravalvular aortic stenosis associated with Williams syndrome was admitted to our hospital for intensive treatment for intractable infective endocarditis. The patient had a history of percutaneous balloon valvuloplasty for aortic stenosis in 1992. He was well until late in 1999, when he had a high temperature after dental work-up. The diagnosis was infective endocarditis but antibiotic therapy was not effective. He was transferred to our clinic. Transthoracic echocardiography demonstrated bicuspid aortic valve, supraaortic stenosis, mitral valve prolapse with severe regurgitation and scattered vegetations on the anterior mitral and aortic valves. In addition, transesophageal echocardiography showed innumerable mobile vegetations located from Valsalva's sinus to the descending aorta. Aortic root and arch replacement with a homograft and mitral valve replacement with an artificial valve were successfully performed to eliminate the infective endocarditis. In the present patient, the flow jet across the supraaortic stenosis seemed to cause a predisposition to severe endocarditis. Record Date Created: 20020808
Record 5Gene structure and genetic localization of the PCLO gene encoding the presynaptic active zone protein Piccolo. Fenster Steven; Garner Craig Department of Neurobiology, University of Alabama at Birmingham, 1719 6th Avenue South CIRC 589, 35294-0021, Birmingham, AL, USA International journal of developmental neuroscience : the official journal of the International Society for Developmental Neuroscience (England) Jun 2002, 20 (3-5) p161, ISSN 0736-5748 Document type: Journal Article Languages: ENGLISH Main Citation Owner: NLM Record type: In Process
Piccolo belongs to a family of presynaptic cytoskeletal proteins likely to be involved in the assembly and function of presynaptic active zones as sites of neurotransmitter release. Given that abnormalities in the formation of synaptic junctions are thought to contribute to cognitive dysfunction during brain development, we have analyzed and compared the gene structure of the Piccolo gene, PCLO, from humans and mice and determined their chromosomal localization. A comparison of the deduced amino acid sequence of cDNA clones encoding Piccolo from human, mouse, rat and chicken reveals the presence of distinct homology domains. Only subsets of these are also present in the structurally related active zone protein Bassoon indicating that Piccolo and Bassoon perform related but distinct functions at active zones. Characterization of the PCLO gene reveals the presence of 25 coding exons spread over 380kb of genomic DNA. The human PCLO gene maps to 7q11.23-q21.3, a region of chromosome 7 implicated as a linkage site for autism and Williams Syndrome suggesting that alterations in the expression of Piccolo or the PCLO gene could contribute to developmental disabilities and mental retardation. Record Date Created: 20020814
Record 6Abnormal spine morphology and enhanced LTP in LIMK-1 knockout mice. Meng Yanghong; Zhang Yu; Tregoubov Vitali; Janus Christopher; Cruz Luis; Jackson Mike; Lu Wei Yang; MacDonald John F; Wang Jay Y; Falls Douglas L; Jia Zhengping Program in Brain and Behavior, The Hospital for Sick Children, 555 University Avenue, Toronto, Ontario, Canada M5G 1X8. Neuron (United States) Jul 3 2002, 35 (1) p121-33, ISSN 0896-6273 Comment in Neuron. 2002 Jul 3;35(1) 3-5; Comment in PMID 12123600 Document type: Journal Article Languages: ENGLISH Main Citation Owner: NLM Record type: Completed
In vitro studies indicate a role for the LIM kinase family in the regulation of cofilin phosphorylation and actin dynamics. In addition, abnormal expression of LIMK-1 is associated with Williams syndrome, a mental disorder with profound deficits in visuospatial cognition. However, the in vivo function of this family of kinases remains elusive. Using LIMK-1 knockout mice, we demonstrate a significant role for LIMK-1 in vivo in regulating cofilin and the actin cytoskeleton. Furthermore, we show that the knockout mice exhibited significant abnormalities in spine morphology and in synaptic function, including enhanced hippocampal long-term potentiation. The knockout mice also showed altered fear responses and spatial learning. These results indicate that LIMK-1 plays a critical role in dendritic spine morphogenesis and brain function. Record Date Created: 20020718
Record 7Face and place processing in Williams syndrome: evidence for a dorsal-ventral dissociation. Paul Brianna M; Stiles Joan; Passarotti Alessandra; Bavar Nasim; Bellugi Ursula Joint Doctoral Program in Clinical Psychology, San Diego State University/University of California, USA. Neuroreport (England) Jul 2 2002, 13 (9) p1115-9, ISSN 0959-4965 Document type: Journal Article Languages: ENGLISH Main Citation Owner: NLM Record type: In Process
Individuals with Williams syndrome (WMS) show an interesting dissociation of ability within the visuospatial domain, particularly between face perception and other visuospatial tasks. In this population, using tasks matched for stimuli, required response, and difficulty (for controls) is critical when comparing performance across these areas. We compared WMS individuals with a sample of typically developing 8- and 9-year-old children, and with a sample of adults, closer to the WMS participants in chronological age, in order to investigate performance across two precisely matched perceptual tasks, one assessing face processing and the other assessing proficiency in processing stimuli location. The pattern of performance seen in WMS, but not in controls, implicates a specific deficit of dorsal stream functioning in this syndrome. Record Date Created: 20020801
Record 8Identification of additional transcripts in the Williams-Beuren syndrome critical region. Merla Giuseppe; Ucla Catherine; Guipponi Michel; Reymond Alexandre Division of Medical Genetics, University of Geneva Medical School, CMU, 1 Rue Michel Servet, 1211 Geneva 4, Switzerland. Human genetics (Germany) May 2002, 110 (5) p429-38, ISSN 0340-6717 Document type: Journal Article Languages: ENGLISH Main Citation Owner: NLM Record type: Completed Williams-Beuren syndrome (WBS) is a developmental disorder associated with haploinsufficiency of multiple genes at 7q11.23. Here, we report the characterization of WBSCR16, WBSCR17, WBSCR18, WBSCR20A, WBSCR20B, WBSCR20C, WBSCR21, WBSCR22, and WBSCR23, nine novel genes contained in the WBS commonly deleted region or its flanking sequences. They encode an RCC1-like G-exchanging factor, an N-acetylgalactosaminyltransferase, a DNAJ-like chaperone, NOL1/NOP2/sun domain-containing proteins, a methyltransferase, or proteins with no known homologies. Haploinsufficiency of these newly identified WBSCR genes may contribute to certain of the WBS phenotypical features. Record Date Created: 20020619
Record 9Adjunct diagnostic test for Angelman syndrome: the tuning fork response. Hall Bryan D American journal of medical genetics (United States) May 1 2002, 109 (3) p238-40, ISSN 0148-7299 Document type: Letter Languages: ENGLISH Main Citation Owner: NLM Record type: Completed Record Date Created: 20020523
Record 10Cardiovascular manifestations in 75 patients with Williams syndrome. Eronen M; Peippo M; Hiippala A; Raatikka M; Arvio M; Johansson R; Kahkonen M The Hospital for Children and Adolescents, Division of Paediatric Cardiology, University of Helsinki, Finland. [email protected] Journal of medical genetics (England) Aug 2002, 39 (8) p554-8, ISSN 1468-6244 Document type: Journal Article Languages: ENGLISH Main Citation Owner: NLM Record type: In Process
OBJECTIVE: The prevalence and types of various cardiovascular diseases in different age groups as well as the outcomes of cardiac surgery and other interventions were assessed in a population of 75 Williams syndrome (WS) patients aged 4 months to 76 years (median 22.7 years). STUDY DESIGN: The diagnosis of WS was in each case confirmed by the clinical phenotype and by a FISH test showing elastin hemizygosity. Clinical and operative data were collected from all hospitals where the patients had been treated. RESULTS: Cardiovascular symptoms were evident in 35 of 75 (47%) WS children at birth. During follow up, 44 of 75 (53%) WS patients were found to have cardiovascular defects. Among them, the definitive diagnosis was made before 1 year of age in 23 (52%) infants, between 1 year and 15 years of age in 14 (32%) children, and older than 15 years of age in 7 (16%) adults. Multiple obstructive cardiovascular diseases were found in six infants. Supravalvular aortic stenosis (SVAS) was diagnosed in 32/44 (73%), pulmonary arterial stenosis (PAS) in 18/44 (41%), aortic or mitral valve defect in 5/44 (11 %) of cases, and tetralogy of Fallot in one (2%) case. Altogether, 17/44 (39 %) underwent surgery or intervention. Surgery was most frequently performed in the infant group (6% v 21% v 0%, p=0.004). After 1 year of age, seven patients underwent SVAS relief and two cases PAS relief. Postoperatively there was no mortality (median follow up time 6.9 years). Arterial hypertension was found in 55% of adults. In three adults, arterial vasculopathy was not diagnosed until necropsy. CONCLUSIONS: Our data indicate the following in WS. Cardiac symptoms are common in neonates. Heart disease diagnosed in infancy frequently requires operation. After 1 year of age, PAS tends to improve and SVAS to progress. Life long cardiac follow up is necessary because of the risks of developing vasculopathy or arterial hypertension. Record Date Created: 20020805
Record 11Disruption of the elastin gene in adult Williams syndrome is accompanied by a paradoxical reduction in arterial stiffness. Lacolley Patrick; Boutouyrie Pierre; Glukhova Marina; Daniel Lamaziere Jean-Marie; Plouin Pierre-Francois; Bruneval Patrick; Vuong Phat; Corvol Pierre; Laurent Stephane INSERM EMI-U 0107, 15 rue de l'ecole de medecine, 75270 Paris cedex 06, France. Clinical science (London, England : 1979) (England) Jul 2002, 103 (1) p21-9, ISSN 0143-5221 Document type: Journal Article Languages: ENGLISH Main Citation Owner: NLM Record type: Completed
Although the aetiology of Williams syndrome (WS) is related to elastin gene disruption, its pathogenesis remains unknown, particularly that of vascular lesions. The aim of the present study was to compare the elastic properties of three WS patients with age- and gender-matched normotensive and hypertensive controls. Common carotid arteries of WS patients had a higher distensibility, a thicker intima-media and a lower elastic modulus. Electron microscopy studies of one WS renal artery showed major abnormalities of the elastic fibres, which displayed a reticular structure and a thickening of the internal elastic lamina, whereas the ultrastructure of elastic fibres was normal in a control subadventitial muscular fibrodysplasia. In this WS arterial stenosis, we studied the expression patterns of several major smooth muscle (SM) phenotypic markers using immunofluorescence and used a normal renal artery as a control. In WS, SM-alpha-actin- and myosin-heavy-chain-positive cells contained low amounts of heavy caldesmon, and laminin-beta1 chain was expressed into the basement membranes, indicating a less differentiated phenotype. In conclusion, in WS patients, the carotid artery wall was abnormally distensible and thick, and major ultrastructural abnormalities of elastic fibres were observed in association with smooth muscle cell de-differentiation. These results indicate that the haplo-insufficiency of the elastin gene in WS patients leads to abnormal elastic fibre assembly within the media. Arterial wall hypertrophy found with a primary defect in elastin may represent a major factor responsible for increased distensibility. We suggest that, in WS, the increased proliferative response and the associated de-differentiation process represent two important mechanisms underlying the matrix accumulation and the development of arterial stenosis. Record Date Created: 20020703
Record 12Early categorization abilities in young children with Williams syndrome. Nazzi Thierry; Karmiloff-Smith Annette 1Neurocognitive Development Unit, Institute of Child Health, London, UK; 2Laboratoire Cognition et Developpement, CNRS, Universite Paris 5, 71 Avenue Edouard Vaillant, 92774 Boulogne Billancourt Cedex, France. Neuroreport (England) Jul 19 2002, 13 (10) p1259-62, ISSN 0959-4965 Document type: Journal Article Languages: ENGLISH Main Citation Owner: NLM Record type: In Process
The present study investigated whether 2- to 6-year-old children with Williams syndrome can form new object categories based on either visual or verbal information alone. Children were presented with six triads of objects. In each triad, two objects either shared visual properties, or were given the same name. Following the presentation of each triad, categorization based on the shared visual or verbal property was evaluated through object manipulation. While the children categorized the objects according to visual cues, they failed to use the verbal cues. These results contrast with previous research showing that typically developing toddlers, who were much younger than the children with Williams syndrome and much less advanced in their vocabulary development, could perform both types of categorization. The present study hence supports the claim that vocabulary acquisition in Williams syndrome develops atypically. Record Date Created: 20020801
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