Williams Syndrome: A disorder caused by hemizygous microdeletion of about 28 genes on chromosome 7q11.23, including the ELASTIN gene. Clinical manifestations include SUPRAVALVULAR AORTIC STENOSIS; MENTAL RETARDATION; elfin facies; impaired visuospatial constructive abilities; and transient HYPERCALCEMIA in infancy. The condition affects both sexes, with onset at birth or in early infancy.Aortic Stenosis, Supravalvular: A pathological constriction occurring in the region above the AORTIC VALVE. It is characterized by restricted outflow from the LEFT VENTRICLE into the AORTA.Syndrome: A characteristic symptom complex.Chromosomes, Human, Pair 7: A specific pair of GROUP C CHROMOSOMES of the human chromosome classification.ElastinFacies: The appearance of the face that is often characteristic of a disease or pathological condition, as the elfin facies of WILLIAMS SYNDROME or the mongoloid facies of DOWN SYNDROME. (Random House Unabridged Dictionary, 2d ed)Lim Kinases: Serine protein kinases involved in the regulation of ACTIN polymerization and MICROTUBULE disassembly. Their activity is regulated by phosphorylation of a threonine residue within the activation loop by intracellular signaling kinases such as P21-ACTIVATED KINASES and by RHO KINASE.Personal Construct Theory: A psychological theory based on dimensions or categories used by a given person in describing or explaining the personality and behavior of others or of himself. The basic idea is that different people will use consistently different categories. The theory was formulated in the fifties by George Kelly. Two tests devised by him are the role construct repertory test and the repertory grid test. (From Stuart Sutherland, The International Dictionary of Psychology, 1989)Nervous System Malformations: Structural abnormalities of the central or peripheral nervous system resulting primarily from defects of embryogenesis.Intellectual Disability: Subnormal intellectual functioning which originates during the developmental period. This has multiple potential etiologies, including genetic defects and perinatal insults. Intelligence quotient (IQ) scores are commonly used to determine whether an individual has an intellectual disability. IQ scores between 70 and 79 are in the borderline range. Scores below 67 are in the disabled range. (from Joynt, Clinical Neurology, 1992, Ch55, p28)Face: The anterior portion of the head that includes the skin, muscles, and structures of the forehead, eyes, nose, mouth, cheeks, and jaw.Down Syndrome: A chromosome disorder associated either with an extra chromosome 21 or an effective trisomy for chromosome 21. Clinical manifestations include hypotonia, short stature, brachycephaly, upslanting palpebral fissures, epicanthus, Brushfield spots on the iris, protruding tongue, small ears, short, broad hands, fifth finger clinodactyly, Simian crease, and moderate to severe INTELLECTUAL DISABILITY. Cardiac and gastrointestinal malformations, a marked increase in the incidence of LEUKEMIA, and the early onset of ALZHEIMER DISEASE are also associated with this condition. Pathologic features include the development of NEUROFIBRILLARY TANGLES in neurons and the deposition of AMYLOID BETA-PROTEIN, similar to the pathology of ALZHEIMER DISEASE. (Menkes, Textbook of Child Neurology, 5th ed, p213)Cardiovascular Abnormalities: Congenital, inherited, or acquired anomalies of the CARDIOVASCULAR SYSTEM, including the HEART and BLOOD VESSELS.History, 19th Century: Time period from 1801 through 1900 of the common era.Perceptual Disorders: Cognitive disorders characterized by an impaired ability to perceive the nature of objects or concepts through use of the sense organs. These include spatial neglect syndromes, where an individual does not attend to visual, auditory, or sensory stimuli presented from one side of the body.Creativity: The ability to generate new ideas or images.Intelligence: The ability to learn and to deal with new situations and to deal effectively with tasks involving abstractions.Abnormalities, MultipleIn Situ Hybridization, Fluorescence: A type of IN SITU HYBRIDIZATION in which target sequences are stained with fluorescent dye so their location and size can be determined using fluorescence microscopy. This staining is sufficiently distinct that the hybridization signal can be seen both in metaphase spreads and in interphase nuclei.History, 17th Century: Time period from 1601 through 1700 of the common era.
Austin B. Williams: Austin Beatty Williams (October 17, 1919 – October 27, 1999) was an American carcinologist, "the acknowledged expert on and leader in studies of the systematics of eastern American decapod crustaceans".}}Malformative syndrome: A malformative syndrome (or malformation syndrome) is a recognizable pattern of congenital anomalies that are known or thought to be causally related (VIIth International Congress on Human Genetics).Elastin: Elastin is a highly elastic protein in connective tissue and allows many tissues in the body to resume their shape after stretching or contracting. Elastin helps skin to return to its original position when it is poked or pinched.Facies (medical): In medical contexts, a facies is a distinctive facial expression or appearance associated with specific medical conditions.Pyr1Hyperphosphatasia with mental retardation syndrome: Hyperphosphatasia with mental retardation syndrome, HPMRS, also known as Mabry syndrome, has been described in patients recruited on four continents world-wide. Mabry syndrome was confirmed to represent an autosomal recessive syndrome characterized by severe mental retardation, considerably elevated serum levels of alkaline phosphatase, hypoplastic terminal phalanges, and distinct facial features that include: hypertelorism, a broad nasal bridge and a rectangular face.Face.com: Face.com was a Tel Aviv-based technology company that developed a platform for efficient and accurate facial recognition in photos uploaded via web and mobile applications.National Down Syndrome SocietyDouble aortic arch: Double aortic arch (DAA) is a relatively rare congenital cardiovascular malformation. DAA is an anomaly of the aortic arch in which two aortic arches form a complete vascular ring that can compress the trachea and/or esophagus.Newington Green Unitarian ChurchHemispatial neglectCreativity and mental illness: Parallels can be drawn to connect creativity to Major Mental Illnesses including: Bipolar Disorder, Schizophrenia, Depression, Anxiety Disorder, and ADHD. For example, numerous studies have demonstrated correlations between creative occupations and people living with mental illness.Evolution of human intelligence: The evolution of human intelligence refers to a set of theories that attempt to explain how human intelligence has evolved and are closely tied to the evolution of the human brain and to the origin of language.Epicanthic fold: Epicanthic fold (), epicanthal fold, epicanthus, or simply eye fold are names for a skin fold of the upper eyelid, covering the inner corner (medial canthus) of the eye. Other names for this trait include plica palpebronasalis and palpebronasal fold..Discoverer 23
(1/254) Comparative mapping of the region of human chromosome 7 deleted in williams syndrome.
Williams syndrome (WS) is a complex developmental disorder resulting from the deletion of a large (approximately 1.5-2 Mb) segment of human chromosome 7q11.23. Physical mapping studies have revealed that this deleted region, which contains a number of known genes, is flanked by several large, nearly identical blocks of DNA. The presence of such highly related DNA segments in close physical proximity to one another has hampered efforts to elucidate the precise long-range organization of this segment of chromosome 7. To gain insight about the structure and evolutionary origins of this important and complex genomic region, we have constructed a fully contiguous bacterial artificial chromosome (BAC) and P1-derived artificial chromosome (PAC) contig map encompassing the corresponding region on mouse chromosome 5. In contrast to the difficulties encountered in constructing a clone-based physical map of the human WS region, the BAC/PAC-based map of the mouse WS region was straightforward to construct, with no evidence of large duplicated segments, such as those encountered in the human WS region. To confirm this difference, representative human and mouse BACs were used as probes for performing fluorescence in situ hybridization (FISH) to metaphase and interphase chromosomes. Human BACs derived from the nonunique portion of the WS region hybridized to multiple, closely spaced regions on human chromosome 7q11.23. In contrast, corresponding mouse BACs hybridized to a single site on mouse chromosome 5. Furthermore, FISH analysis revealed the presence of duplicated segments within the WS region of various nonhuman primates (chimpanzee, gorilla, orangutan, and gibbon). Hybridization was also noted at the genomic locations corresponding to human chromosome 7p22 and 7q22 in human, chimpanzee, and gorilla, but not in the other animal species examined. Together, these results indicate that the WS region is associated with large, duplicated blocks of DNA on human chromosome 7q11.23 as well as the corresponding genomic regions of other nonhuman primates. However, such duplications are not present in the mouse. (+info)
(2/254) Williams-Beuren syndrome: genes and mechanisms.
Williams-Beuren syndrome (WBS; OMIM 194050) is caused by heterozygous deletions of approximately 1.6 Mb of chromosomal sub-band 7q11.23. The deletions are rather uniform in size as they arise spontaneously by inter- or intrachromosomal crossover events within misaligned duplicated regions of high sequence identity that flank the typical deletion. This review will discuss the status of the molecular characterization of the deletion and flanking regions, the genes identified in the deletion region and their possible roles in generating the complex multi-system clinical phenotype. (+info)
(3/254) A transcription factor involved in skeletal muscle gene expression is deleted in patients with Williams syndrome.
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. (+info)
(4/254) Second-order belief attribution in Williams syndrome: intact or impaired?
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. (+info)
(5/254) Cognitive modularity and genetic disorders.
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. (+info)
(6/254) A physical map, including a BAC/PAC clone contig, of the Williams-Beuren syndrome--deletion region at 7q11.23.
Williams-Beuren syndrome (WBS) is a developmental disorder caused by haploinsufficiency for genes in a 2-cM region of chromosome band 7q11.23. With the exception of vascular stenoses due to deletion of the elastin gene, the various features of WBS have not yet been attributed to specific genes. Although >/=16 genes have been identified within the WBS deletion, completion of a physical map of the region has been difficult because of the large duplicated regions flanking the deletion. We present a physical map of the WBS deletion and flanking regions, based on assembly of a bacterial artificial chromosome/P1-derived artificial chromosome contig, analysis of high-throughput genome-sequence data, and long-range restriction mapping of genomic and cloned DNA by pulsed-field gel electrophoresis. Our map encompasses 3 Mb, including 1.6 Mb within the deletion. Two large duplicons, flanking the deletion, of >/=320 kb contain unique sequence elements from the internal border regions of the deletion, such as sequences from GTF2I (telomeric) and FKBP6 (centromeric). A third copy of this duplicon exists in inverted orientation distal to the telomeric flanking one. These duplicons show stronger sequence conservation with regard to each other than to the presumptive ancestral loci within the common deletion region. Sequence elements originating from beyond 7q11.23 are also present in these duplicons. Although the duplicons are not present in mice, the order of the single-copy genes in the conserved syntenic region of mouse chromosome 5 is inverted relative to the human map. A model is presented for a mechanism of WBS-deletion formation, based on the orientation of duplicons' components relative to each other and to the ancestral elements within the deletion region. (+info)
(7/254) Characterization and gene structure of a novel retinoblastoma-protein-associated protein similar to the transcription regulator TFII-I.
Retinoblastoma protein (Rb) is an important regulator of vertebrate cell cycle and development. It functions through a direct interaction with protein factors involved in cell cycle progression and differentiation. In the present study we characterized a novel Rb-associated protein, Cream1, which bound to Rb specifically through a C-terminal region. Cream1 contained 959 amino acid residues and migrated as a protein of approx. 120 kDa on SDS/PAGE. It was a widely expressed nuclear protein with a nuclear localization signal resembling that of the large T antigen of simian virus 40. Its primary sequence was characteristic of five direct repeats that were similar to, but distinct from, those of TFII-I, a multifunctional transcription regulator. Three additional regions were also highly conserved in both proteins. Cream1 exhibited an activation activity that was attributed to its N-terminal portion when assayed in yeast. Its relationship with the muscle-enhancer-binding protein MusTRD1 further suggests a role in regulating gene expression. The structural gene, CREAM1, contained 27 exons and spanned more than 150 kb. It was located at human chromosome 7q11.23 in a region deleted for Williams' syndrome, a neurodevelopmental disease with multisystem abnormalities, implying its involvement in certain disorders. Taken together, our results suggest that Cream1 might serve as a positive transcription regulator under the control of Rb. (+info)
(8/254) A family of chromatin remodeling factors related to Williams syndrome transcription factor.
Chromatin remodeling complexes have been implicated in the disruption or reformation of nucleosomal arrays resulting in modulation of transcription, DNA replication, and DNA repair. Here we report the isolation of WCRF, a new chromatin-remodeling complex from HeLa cells. WCRF is composed of two subunits, WCRF135, the human homolog of Drosophila ISWI, and WCRF180, a protein related to the Williams syndrome transcription factor. WCRF180 is a member of a family of proteins sharing a putative heterochromatin localization domain, a PHD finger, and a bromodomain, prevalent in factors involved in regulation of chromatin structure. (+info)