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Record 1Connection between elastin haploinsufficiency and increased cell proliferation in patients with supravalvular aortic stenosis and Williams-Beuren syndrome. Urban Zsolt; Riazi Sheila; Seidl Thomas L; Katahira Jodi; Smoot Leslie B; Chitayat David; Boyd Charles D; Hinek Aleksander Pacific Biomedical Research Center, University of Hawaii, Honolulu, USA. American journal of human genetics (United States) Jul 2002, 71 (1) p30-44, ISSN 0002-9297 Document type: Journal Article Languages: ENGLISH Main Citation Owner: NLM Record type: Completed
To elucidate the pathomechanism leading to obstructive vascular disease in patients with elastin deficiency, we compared both elastogenesis and proliferation rate of cultured aortic smooth-muscle cells (SMCs) and skin fibroblasts from five healthy control subjects, four patients with isolated supravalvular aortic stenosis (SVAS), and five patients with Williams-Beuren syndrome (WBS). Mutations were determined in each patient with SVAS and in each patient with WBS. Three mutations found in patients with SVAS were shown to result in null alleles. RNA blot hybridization, immunostaining, and metabolic labeling experiments demonstrated that SVAS cells and WBS cells have reduced elastin mRNA levels and that they consequently deposit low amounts of insoluble elastin. Although SVAS cells laid down approximately 50% of the elastin made by normal cells, WBS cells deposited only 15% of the elastin made by normal cells. The observed difference in elastin-gene expression was not caused by a difference in the stability of elastin mRNA in SVAS cells compared with WBS cells, but it did indicate that gene-interaction effects may contribute to the complex phenotype observed in patients with WBS. Abnormally low levels of elastin deposition in SVAS cells and in WBS cells were found to coincide with an increase in proliferation rate, which could be reversed by addition of exogenous insoluble elastin. We conclude that insoluble elastin is an important regulator of cellular proliferation. Thus, the reduced net deposition of insoluble elastin in arterial walls of patients with either SVAS or WBS leads to the increased proliferation of arterial SMCs. This results in the formation of multilayer thickening of the tunica media of large arteries and, consequently, in the development of hyperplastic intimal lesions leading to segmental arterial occlusion. Record Date Created: 20020617
Record 2[Syndromes 5. Williams-Beuren Syndrome] Syndromen 5. Het Williams-Beuren-syndroom. Hoff M; van Hagen J M; Baart J A; Vissink A Afdeling Mondziekten, Kaakchirurgie en Bijzondere Tandheelkunde, Academisch Ziekenhuis Groningen, postbus 30.001, 9700 RB Groningen. Nederlands tijdschrift voor tandheelkunde (Netherlands) Oct 1998, 105 (10) p368-9, ISSN 0028-2200 Document type: Journal Article ; English Abstract Languages: DUTCH Main Citation Owner: NLM Record type: Completed
A characteristic facial appearance, mental retardation, growth deficiency, cardiovascular anomalies, and infantile hypercalcemia are major features of the Williams-Beuren syndrome. The dentist can contribute to the (early) diagnosis of this disorder. Record Date Created: 20020403
Record 3Abnormal 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, M5G 1X8, Toronto, Ontario, Canada Neuron (United States) Jul 3 2002, 35 (1) p121-33, ISSN 0896-6273 Document type: Journal Article Languages: ENGLISH Main Citation Owner: NLM Record type: In Process
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 4Shifting attention and joint attention dissociation in williams syndrome: implications for the cerebellum and social deficits in autism. Lincoln Alan; Lai Zona; Jones Wendy Alliant International University, California School of Professional Psychology-San Diego, San Diego, California and Laboratory for Cognitive Neuroscience, The Salk Institute for Biological Studies, La Jolla, CA, USA. Neurocase : case studies in neuropsychology, neuropsychiatry, and behavioural neurology (England) 2002, 8 (3) p226-32, ISSN 1355-4794 Document type: Journal Article Languages: ENGLISH Main Citation Owner: NLM Record type: In Process
An experimental paradigm that assesses one's capacity to perform intermodality attention shifting has proved to be sensitive for persons with cerebellar dysfunction. The basic experiment includes three conditions, auditory focus, visual focus and shift attention. In the auditory focus condition, the participant is instructed to press a joystick button when they hear the target tone and to ignore the other tone and the two visual stimuli. In the visual focus condition, the participant is instructed to press only the button to the target colored square and to ignore the other colored square and the two tones. In the shift attention condition, the participant is instructed to press the button to the first auditory target and then to press to the next visual target. They are instructed to continue to alternate their responses between auditory and visual targets until the trial is complete. Three individuals with Williams Syndrome (WMS), a genetic disorder due to the deletion of the elastin gene, were examined under these experimental conditions. Each participant with WMS had previously completed magnetic resonance imaging, and mid-sagittal area measurements had been made of the vermal lobules I-V and VI-VII. Cases were selected on the basis of cerebellar findings: one case was hypoplastic, one was hyperplastic and one had measurements in a range within one standard deviation of average for normal controls. Each of the WMS participants showed a pattern of being impaired in being able to shift their attention rapidly when cue-to-target intervals were less than 2.5 s. Their performance was very similar to previous reports of persons with cerebellar abnormalities and persons with autism. All three participants improved their target accuracy when given more time to shift their attention. The three participants did not experience performance deficits to either long or short cue-to-target intervals in the auditory focus or visual focus conditions. The results are consistent with the presence of cerebellar dysfunction, and are the first to suggest problems with shifting attention in persons with WMS. However, the three WMS participants demonstrated normal joint attention and had none of the social deficits observed in persons with autism. Record Date Created: 20020716
Record 5A 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: In Process
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 6Elastin mutation is associated with a reduced gain of the baroreceptor--heart rate reflex in patients with Williams syndrome. Girard Arlette; Sidi Daniel; Aggoun Yacine; Laude Dominique; Bonnet Damien; Elghozi Jean-Luc Department de Nephrologie, Hopital Necker, Paris, France. Clinical autonomic research : official journal of the Clinical Autonomic Research Society (England) Apr 2002, 12 (2) p72-7, ISSN 0959-9851 Document type: Journal Article Languages: ENGLISH Main Citation Owner: NLM Record type: In Process
Microdeletion of chromosome 7q, encompassing the elastin locus, has been identified in patients with Williams syndrome (WS). This study tested the hypothesis that loss of medial elastin affects the discharge of baroreceptors and consequently the baroreflex sensitivity (BRS). Eight untreated patients with WS (14.8 +/- 2.4 y, m +/- SEM) were compared to 8 healthy subjects (15.1 +/- 2.3 y). Blood pressure (BP) was recorded using a Finapres monitor in the supine position. Systolic BP (SBP) levels were 117.8 +/- 4.4 mmHg in WS compared to 110.9 +/- 5.7 in controls (ns). Pulse rate (PR, taken as a surrogate for heart rate) was higher in the WS (89.6 +/- 1.0 vs 74.1 +/- 2.3 beats/min in controls, P < 0.01). The variance (total power) of PI variability was reduced in WS subjects. The amplitudes of the low frequency (LF, 0.1 Hz) and high frequency (HF, respiratory) PI component (modulus) were reduced in WS (210.5 +/- 4.3 vs 34.6 +/- 2.6 ms, P = 0.02 for LF, for HF). The gain of the SBP-PI transfer function was diminished in the low frequency (LF, 0.1 Hz) and the HF range as well (5.8 +/- 0.7 vs 12.1 +/- 1.8 ms/mmHg for LF, P < 0.01 and 6.2 +/- 1.0 vs 21.7 +/- 4.6 ms/mmHg for HF, P < 0.01). The BRS obtained with the sequence technique was also reduced in WS (8.2 +/- 0.9 vs 21.5 +/- 2.9 ms/mm Hg in controls, P < 0.001). The percent of beats involved in baroreflex sequences observed in WS was also diminished to 20% compared to 48% in controls (P < 0.001). In conclusion a BRS reduction associated with a PR elevation was observed in normotensive WS subjects. It is likely abnormal elastic fiber assembly at the arterial level alters baroreceptor discharges. Record Date Created: 20020709
Record 7Disruption 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) p21-8, ISSN 0143-5221 Document type: Journal Article Languages: ENGLISH Main Citation Owner: NLM Record type: In Process
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 8Prevalence estimation of Williams syndrome. Stromme Petter; Bjornstad Per G; Ramstad Kjersti Department of Paediatrics, Rikshospitalet, The National Hospital, Oslo, Norway. petter [email protected] Journal of child neurology (United States) Apr 2002, 17 (4) p269-71, ISSN 0883-0738 Document type: Journal Article Languages: ENGLISH Main Citation Owner: NLM Record type: In Process
There are limited population-based data on the occurrence of Williams syndrome. We estimated its prevalence combining data from two investigations. One was an epidemiologic study originally designed to assess the prevalence and etiology of mental retardation among 30,037 Norwegian children born between 1980 and 1985 and living in Akershus County on January 1, 1993. The other investigation was a national survey of Williams syndrome. In the first study, 213 children were referred for evaluation, whereas the second study comprised 57 cases with Williams syndrome born between 1970 and 1992, who were referred for evaluation from all Norwegian counties. The epidemiologic study revealed three children with Williams syndrome, whereas one additional case complying with our demographic criteria was identified in the national survey, thus giving a prevalence of 1 in 7500. In all cases, a typical chromosome 7q11.23 deletion was detected. We also conclude that Williams syndrome is not an uncommon cause of mental retardation, with a prevalence of approximately 6% of patients with genetic etiology. Record Date Created: 20020628
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