Assessment of the influence of background noise on escape-maintained problem behavior and pain behavior in a child with Williams syndrome.
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We examined the influence of background noise on levels of problem behavior and pain behavior under functional analysis conditions for a child with a diagnosis of Williams syndrome and hyperacusis. Background noise was associated with increases in escape-maintained problem behavior and increases in pain behavior such as clasping ears and crying. When the child was fitted with earplugs, there were substantial reductions in both problem and pain behavior under the background noise condition. (+info)
WBSCR14, a gene mapping to the Williams--Beuren syndrome deleted region, is a new member of the Mlx transcription factor network.
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Williams-Beuren syndrome (WBS) is a developmental disorder associated with haploinsufficiency of multiple genes at 7q11.23. Here, we report the functional characterization of WBS critical region gene 14 (WBSCR14), a gene contained in the WBS commonly deleted region. It encodes a basic-helix--loop--helix leucine zipper (bHLHZip) transcription factor of the Myc/Max/Mad superfamily. WBSCR14 is expressed in multiple tissues, including regions of the brain and the intestinal tract. WBSCR14 forms heterodimers with the bHLHZip protein Mlx to bind the DNA sequence CACGTG. Like Max, Mlx has no intrinsic transcriptional activity, but its association with Mad1, Mad4, Mnt or WBSCR14 can repress E-box-dependent transcription. Preliminary results suggest a possible role of WBSCR14 in growth control. Our data support the view that the Max-like bHLHZip protein, Mlx, is a key element of a transcription factor network. We thus suggest that WBSCR14 may contribute to some aspects of the WBS pathology. (+info)
Balloon dilation angioplasty of peripheral pulmonary stenosis associated with Williams syndrome.
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BACKGROUND: Experience of balloon dilation of peripheral pulmonary stenosis (PPS) in Williams syndrome (WS) is limited. METHODS AND RESULTS: Catheterizations in all patients with WS undergoing therapy for PPS from 1984 to 1999 were reviewed. Criteria for successful dilation included an increase >50% in predilation diameter and a decrease >20% in ratio of right ventricular (RV) to aortic (Ao) systolic pressure. Median age and weight were 1.5 years and 9.5 kg. There were 134 dilations during 39 procedures in 25 patients. The success rate for initial dilations was 51%. In multivariate analysis, successful dilation was more likely (1) in distal than in central pulmonary arteries (P=0.02), (2) if the balloon waist resolved with inflation (P=0.001), and (3) with larger balloon/stenosis ratio (P<0.001). RV pressure was unchanged after dilation (96+/-30 versus 97+/-31 mm Hg), primarily because of failure to enlarge central pulmonary arteries. The Ao pressure increased (102+/-14 versus 109+/-19 mm Hg, P=0.03), and the RV/Ao pressure ratio decreased (0.97+/-0.34 versus 0.91+/-0.30, P=0.05). Aneurysms developed after 24 dilations (18%) and were not related to balloon/stenosis ratio. Balloon rupture in 12 dilations produced an aneurysm in all 7 cases when rupture was in a hypoplastic segment. Three patients died, none from pulmonary artery trauma, and all before 1994. CONCLUSIONS: Mortality occurred early in our experience. Despite successful dilation of distal pulmonary arteries, there was modest initial hemodynamic improvement, mainly because of persistent central pulmonary artery obstruction. A serial approach of distal dilations followed by surgical repair of proximal obstruction may be a rational and successful therapy. (+info)
A 1.5 million-base pair inversion polymorphism in families with Williams-Beuren syndrome.
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Williams-Beuren syndrome (WBS) is most often caused by hemizygous deletion of a 1.5-Mb interval encompassing at least 17 genes at 7q11.23 (refs. 1,2). As with many other haploinsufficiency diseases, the mechanism underlying the WBS deletion is thought to be unequal meiotic recombination, probably mediated by the highly homologous DNA that flanks the commonly deleted region. Here, we report the use of interphase fluorescence in situ hybridization (FISH) and pulsed-field gel electrophoresis (PFGE) to identify a genomic polymorphism in families with WBS, consisting of an inversion of the WBS region. We have observed that the inversion is hemizygous in 3 of 11 (27%) atypical affected individuals who show a subset of the WBS phenotypic spectrum but do not carry the typical WBS microdeletion. Two of these individuals also have a parent who carries the inversion. In addition, in 4 of 12 (33%) families with a proband carrying the WBS deletion, we observed the inversion exclusively in the parent transmitting the disease-related chromosome. These results suggest the presence of a newly identified genomic variant within the population that may be associated with the disease. It may result in predisposition to primarily WBS-causing microdeletions, but may also cause translocations and inversions. (+info)
Coeliac disease in Williams syndrome.
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BACKGROUND: Coeliac disease (CD) has been reported in several patients affected by chromosomal disorders, including Down syndrome (DS) and Turner syndrome (TS). CD has also been found in sporadic Williams syndrome (WS) patients. In this study, CD was evaluated in a consecutive series of patients with WS, in order to estimate if the prevalence of CD in WS patients is higher than in the general population. METHODS AND RESULTS: A consecutive series of 63 Italian patients with WS was studied by analysing the dosage of antigliadin antibodies (AGA) IgA and antiendomisium antibodies (AEA). In patients with positive AGA and AEA, small bowel biopsy was performed. The prevalence of CD in our WS population was compared with that estimated in a published series of 17 201 Italian students. Seven WS patients were found to be positive for AGA IgA and AEA. Six of them underwent small bowel biopsy, which invariably disclosed villous atrophy consistent with CD. The prevalence of CD in the present series of WS patients was 9.5% (6/63), compared to 0.54% (1/184) in the Italian students (p<0.001). CONCLUSION: The present results suggest that the prevalence of CD in WS is higher than in the general population and is comparable to that reported in DS and TS. AGA and AEA screening is recommended in patients with WS. (+info)
Implicit versus explicit memory function in children with Down and Williams syndrome.
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The present study was aimed at evaluating implicit memory processes in participants with Williams syndrome and comparing them to children with Down syndrome and to mental-age matched typically developing children. For this purpose, tests of verbal and visuo-perceptual explicit memory, verbal and visual repetition priming as well as procedural learning tasks were administered to 12 participants with Williams syndrome, 14 with Down syndrome and 32 typically developing children. Participants with Williams syndrome showed a level of repetition priming similar to that of mental-age typically developing controls. In contrast, children with Williams syndrome showed a reduced learning rate in the two procedural tasks. As regards children with Down syndrome, we document comparable implicit memory abilities. In contrast, regarding explicit memory, typically developing children performed better than individuals with Down syndrome. This finding is relevant for our knowledge about the qualitative aspects of the anomalous cognitive development in individuals with intellectual disabilities and the neurobiological substrate underlying this development. (+info)
Molecular dissection of DNA sequences and factors involved in slow muscle-specific transcription.
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Transcription is a major regulatory mechanism for the generation of slow- and fast-twitch myofibers. We previously identified an upstream region of the slow TnI gene (slow upstream regulatory element [SURE]) and an intronic region of the fast TnI gene (fast intronic regulatory element [FIRE]) that are sufficient to direct fiber type-specific transcription in transgenic mice. Here we demonstrate that the downstream half of TnI SURE, containing E box, NFAT, MEF-2, and CACC motifs, is sufficient to confer pan-skeletal muscle-specific expression in transgenic mice. However, upstream regions of SURE and FIRE are required for slow and fast fiber type specificity, respectively. By adding back upstream SURE sequences to the pan-muscle-specific enhancer, we delineated a 15-bp region necessary for slow muscle specificity. Using this sequence in a yeast one-hybrid screen, we isolated cDNAs for general transcription factor 3 (GTF3)/muscle TFII-I repeat domain-containing protein 1 (MusTRD1). GTF3 is a multidomain nuclear protein related to initiator element-binding transcription factor TF II-I; the genes for both proteins are deleted in persons with Williams-Beuren syndrome, who often manifest muscle weakness. Gel retardation assays revealed that full-length GTF3, as well as its carboxy-terminal half, specifically bind the bicoid-like motif of SURE (GTTAATCCG). GTF3 expression is neither muscle nor fiber type specific. Its levels are highest during a period of fetal development that coincides with the emergence of specific fiber types and transiently increases in regenerating muscles damaged by bupivacaine. We further show that transcription from TnI SURE is repressed by GTF3 when overexpressed in electroporated adult soleus muscles. These results suggest a role for GTF3 as a regulator of slow TnI expression during early stages of muscle development and suggest how it could contribute to Williams-Beuren syndrome. (+info)
Online data collection with special populations over the World Wide Web.
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The quick ascendance of the World Wide Web as the dominant vehicle for internet communication has recently made experimentation in a multimedia environment feasible on the Internet. Although web sites containing online psychology demonstrations and experiments for non-handicapped individuals have appeared in recent years (especially in the areas of cognitive and social psychology), there appear to have been few attempts to conduct online experimentation with special populations. We recently completed two online pilot studies of families with Down syndrome or Williams syndrome members: a) A survey that asks (via Likert rating scales, adjective checklists, multiple-choice style questions, and text-entry boxes) about family background, computer use, and temperament of the special needs family member; and b) An experiment (completed by an individual with special needs) that includes auditory and visual digit span tasks and a memory-for-orientation task in which responses are entered via mouse clicks. Recruiting began with e-mail announcements to representative Down syndrome and Williams syndrome discussion groups, listserves, and bulletin boards, and submission of the project's URL (http://www.cofc.edu/~marcellm/testaw.htm) and key indexing terms to selected search engines. This paper reviews technical aspects of developing the online programmes as well as the strengths and weaknesses of online vs. traditional laboratory-based research in relation to issues such as experimental control, delivery of instructions, experimenter bias, participant recruitment, sample heterogeneity, generalization, attrition, privacy, financial costs, data integrity, and ethics. We conclude by offering our thoughts on two ways of implementing online experimentation with special populations: a) Using a remote parent 'helper' as a proxy to work with the target individual; and b) Collaborating with professional colleagues in Web-based projects conducted in traditional laboratory settings. (+info)