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Record 1Adaptive behavior of 4- through 8-year-old children with Williams syndrome. Mervis CB; Klein-Tasman BP; Mastin ME Department of Psychological and Brain Sciences, University of Louisville, KY 40292, USA. [email protected] American journal of mental retardation (United States) Jan 2001, 106 (1) p82-93, ISSN 0895-8017 Languages: ENGLISH Document type: Journal Article
The adaptive behavior of forty-one 4- through 8-year-olds with Williams syndrome was assessed using the Vineland Adaptive Behavior Scales-Interview Edition. Based on the cognitive and personality profiles characteristic of children with this syndrome, we predicted that the domains of Socialization and Communication would be relative strengths, whereas Daily Living Skills and Motor Skills would be relative weaknesses. We also expected that Socialization Skills would be more advanced than Communication skills, and that within the Socialization domain, interpersonal skills would be stronger than play/leisure or coping skills. All predictions were confirmed. Adaptive behavior standard score was not related to CA. The children earned similar overall standard scores on the Vineland and the Differential Ability Scales. Interrelations among adaptive behavior, cognitive abilities, and personality characteristics are discussed.
Record 2Williams syndrome: From genotype through to the cognitive phenotype. Donnai D; Karmiloff-Smith A American journal of medical genetics (United States) summer 2000, 97 (2) p164-71, ISSN 0148-7299 Languages: ENGLISH Document type: Journal Article
Williams syndrome, due to a contiguous gene deletion at 7q11.23, is associated with a distinctive facial appearance, cardiac abnormalities, infantile hypercalcemia, and growth and developmental retardation. The deletion is approximately 1.5Mb and includes approximately 17 genes. Large repeats containing genes and pseudogenes flank the deletion breakpoints, and the mutation mechanism commonly appears to be unequal meiotic recombination. Elastin hemizygosity is associated with supravalvular aortic stenosis and other vascular stenoses. LIM Kinase 1 hemizygosity may contribute to the characteristic cognitive profile. The relationship of the other deleted genes to phenotypic features is not known. People with Williams syndrome tend to be over friendly-though anxious-and lack social judgement skills. They exhibit an uneven cognitive-linguistic profile together with mild to severe mental retardation. Analysis of the cognitive phenotype based on analyses of the mental processes underlying overt behavior demonstrates major differences between normal and WS subjects although for some areas, such as face processing, WS subjects can achieve near normal scores. Cognitive analysis of patients with small deletions in 7q11.23 which include elastin and LIM Kinase 1 have revealed varying results and it is premature to draw genotype-phenotype correlations. Am. J. Med. Genet. (Semin. Med. Genet.) 97:164-171, 2000. Copyright 2000 Wiley-Liss, Inc.
Record 3[Clinical aspects and genetics of Williams-Beuren syndrome. Clinical and molecular genetic study of 44 patients with suspected Williams-Beuren syndrome] Klinik und Genetik des Williams-Beuren-Syndroms. Klinische und molekulargenetische Untersuchung von 44 Patienten mit Verdacht auf WBS. von Beust G; Laccone FA; del Pilar Andrino M; Wessel A Institut fur Humangenetik, Universitat Gottingen. Klinische Padiatrie (Germany) Nov-Dec 2000, 212 (6) p299-307, ISSN 0300-8630 Languages: GERMAN Document type: Journal Article ; English Abstract
BACKGROUND: The suspected diagnosis of Williams-Beuren syndrome (WBS), which is a retardation syndrome with great clinical variability, was cause for comparison of molecular genetic, molecular cytogenetic analysis to clinical symptoms. The results of the genetical analysis of a microdeletion of the elastin gene region on chromosome 7 were compared to the clinical symptoms. Are there any differences between symptoms in case of deletion or non-deletion? How informative are the molecular genetic, molecular cytogenetic analysis? PATIENTS AND METHODS: 44 patients with suspected diagnosis of WBS were examined using molecular genetic and molecular cytogenetic methods. The clinical symptoms as general symptoms, heart anomaly, dysmorphic signs and unusual neurobehavioural features were reported during clinical investigation in standardized questionnaires. The genomic DNA of the patients and their parents was analyzed using microsatellite markers. In some cases (e.g. uninformative microsatellite studies) we also used fluorescence in situ hybridization (FISH) with an elastin gene probe and performed a conventional chromosome banding analysis. RESULTS: 15 patients had a microdeletion. 4 patients had a deletion of the paternal allel and 7 patients showed the deletion of the maternal allel. The polymorphisms were of limited informativeness. In 2 cases microsatellite analysis was not able to determine whether the paternal or the maternal allel had been lost. In 2 cases the microsatellite analysis was uninformative so that FISH analysis was performed. All FISH analysis performed had an informative result. 80% of the children with a microdeletion of chromosome 7q11.23 showed the typical dysmorphic signs, 70% exhibited the typical WBS behaviour pattern, 50% had a specific heart anomaly. In contrast, in the group of children without a chromosomal microdeletion only 30-40% showed typical dysmorphic signs, only 10% had a typical heart anomaly and none of them showed specific behavioural changes. We found no indication to association of specific symptoms with paternal versus maternal origin of the deletion. The FISH analysis combined with a conventional chromosome banding analysis is very informative for diagnostic values. The results are compared to data of literature. CONCLUSIONS: Children with developmental retardation and WBS dysmorphic signs and an unusual behaviour should be examined by a molecular cytogenetic FISH analysis. If a microdeletion of band 7q11.23 is found a special cardiologic examination should be offered.
Record 4Elastin: mutational spectrum in supravalvular aortic stenosis. Metcalfe K; Rucka AK; Smoot L; Hofstadler G; Tuzler G; McKeown P; Siu V; Rauch A; Dean J; Dennis N; Ellis I; Reardon W; Cytrynbaum C; Osborne L; Yates JR; Read AP; Donnai D; Tassabehji M University Department of Medical Genetics and Regional Genetics Service, St Mary's Hospital, Manchester, UK. European journal of human genetics (England) Dec 2000, 8 (12) p955-63, ISSN 1018-4813 Languages: ENGLISH Document type: Journal Article
Supravalvular aortic stenosis (SVAS) is a congenital narrowing of the ascending aorta which can occur sporadically, as an autosomal dominant condition, or as one component of Williams syndrome. SVAS is caused by translocations, gross deletions and point mutations that disrupt the elastin gene (ELN) on 7q11.23. Functional hemizygosity for elastin is known to be the cause of SVAS in patients with gross chromosomal abnormalities involving ELN. However, the pathogenic mechanisms of point mutations are less clear. One hundred patients with diagnosed SVAS and normal karyotypes were screened for mutations in the elastin gene to further elucidate the molecular pathology of the disorder. Mutations associated with the vascular disease were detected in 35 patients, and included nonsense, frameshift, translation initiation and splice site mutations. The four missense mutations identified are the first of this type to be associated with SVAS. Here we describe the spectrum of mutations occurring in familial and sporadic SVAS and attempt to define the mutational mechanisms involved in SVAS. SVAS shows variable penetrance within families but the progressive nature of the disorder in some cases, makes identification of the molecular lesions important for future preventative treatments.
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