Disease relevance of Williams Syndrome

• We focus on cortical and subcortical changes observed in healthy children, and contrast them with abnormal developmental changes in early-onset schizophrenia, fetal alcohol syndrome, attention-deficit-hyperactivity disorder (ADHD) and Williams syndrome [1].
• Hemizygosity at the NCF1 gene in patients with Williams-Beuren syndrome decreases their risk of hypertension [2].
• 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 [3].
• Fluorescence in situ hybridisation (FISH) and conventional chromosome analysis were performed on a series of 52 patients with classical Williams-Beuren syndrome (WBS), suspected WBS, or supravalvular aortic stenosis (SVAS) [4].
• The nature of the spatial representations that underlie simple visually guided actions early in life was investigated in toddlers with Williams syndrome (WS), Down syndrome (DS), and healthy chronological age- and mental age-matched controls, through the use of a "double-step" saccade paradigm [5].

Psychiatry related information on Williams Syndrome

• OBJECTIVE: Williams syndrome (WS) is associated with neurobehavioral abnormalities that include irritability and attention-deficit/hyperactivity disorder [6].
• In recent studies children with Williams-Beuren syndrome (WBS) have been characterized as having a distinct neuropsychological profile with verbal abilities being superior to visuo-spatial and motor skills [7].
• Serum NGF was measured in normally developing control children (n=26) and in individuals affected by congenital syndromes associated with learning disability: either Williams syndrome (WS; n=12) or Down syndrome (DS; n=21) [8].
• Age-associated changes on measures of episodic and working memory were examined in 15 adults with Williams Syndrome (WS; M age = 48.3 years, SD = 14.7; M IQ = 62.9, SD = 8.5) and their performance was compared to that of 33 adults with mental retardation (MR) with unspecified etiologies (M age = 54.2 years, SD = 8.9; M IQ = 61.7, SD = 6.5) [9].
• This study explored self concepts in matched groups of adolescents and adults with Williams syndrome (WS) and Prader-Willi syndrome (PWS), using Damon and Hart's semi-structured interview [10].

High impact information on Williams Syndrome

• Furthermore, overexpression of WSTF could restore the impaired recruitment of VDR to vitamin D regulated promoters in fibroblasts from Williams syndrome patients [11].
• Targeted mutation of Cyln2 in the Williams syndrome critical region links CLIP-115 haploinsufficiency to neurodevelopmental abnormalities in mice [12].
• 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) [13].
• LIM-kinase deleted in Williams syndrome [14].
• Hemizygosity at the elastin locus in a developmental disorder, Williams syndrome [15].

Chemical compound and disease context of Williams Syndrome

• Abnormal regulation of circulating 25-hydroxyvitamin D in the Williams syndrome [16].
• This spared cognitive capacity may be linked to the relative sparing of limbic-cerebellar neural substrate in Williams syndrome, which is also connected to cortico-frontal regions that are known to be involved in understanding complex mental states [17].
• Decreased serine levels were found in plasma and cerebrospinal fluid (CSF) of a boy with pre- and postnatal growth retardation, moderate psychomotor retardation, and facial dysmorphism suggestive of Williams syndrome [18].
• Increased 1,25-dihydroxyvitamin D levels and decreased basal and calcium-stimulated calcitonin serum levels have been found in children with Williams-Beuren syndrome (WBS) [19].
• A girl with Williams syndrome (WS) presented with elevated thyrotropin (TSH) levels (7.0 microU/ml), normal free thyroid hormone concentrations, and absent antithyroid autoantibodies [20].

Biological context of Williams Syndrome

• A unique opportunity to understand genetic determinants of cognition is offered by Williams syndrome (WS), a well-characterized hemideletion on chromosome 7q11.23 that causes extreme, specific weakness in visuospatial construction (the ability to visualize an object as a set of parts or construct a replica) [21].
• To investigate the frequency of deletions of the elastin gene in patients with Williams syndrome (WS), we screened 44 patients by both FISH and PCR amplification of a dinucleotide repeat polymorphism [22].
• The recent findings that knockout mice lacking LIMK1 or CLIP-115 have distinct neurological and behavioural phenotypes, indicates that cytoskeletal defects might play a role in the development of neurological symptoms in Williams Syndrome patients [23].
• Heterozygous mice (the same frizzled 9 genotype as Williams syndrome patients) were intermediate between wild type and null mice for all developmental neuronanatomic defects [24].
• Genomic organization of the genes Gtf2ird1, Gtf2i, and Ncf1 at the mouse chromosome 5 region syntenic to the human chromosome 7q11.23 Williams syndrome critical region [25].

Anatomical context of Williams Syndrome

• Frizzled 9 is selectively expressed in the hippocampus and is one of about 20 genes typically deleted in Williams syndrome [24].
• As the largest interhemispheric commissure in the brain, the corpus callosum is of particular interest in disorders that may preferentially affect white matter development such as Williams syndrome (WS) [26].
• Vocal cord abnormalities in Williams syndrome: a further manifestation of elastin deficiency [27].
• Parietal lobe impairment is hypothesized to contribute to the dramatic visual-spatial deficits in Williams syndrome (WS) [28].
• A 7 year old girl and her mother have typical phenotypic features of the Williams' (elfin facies) syndrome, and both have only mild mitral regurgitation with mitral valve prolapse (MVP) [29].

Gene context of Williams Syndrome

• Human WSTF, which is encoded by one of multiple genes that is deleted in Williams syndrome individuals, is the only currently known mammalian protein with each of the conserved motifs in Acf1 [30].
• The Williams Syndrome Transcription Factor (WSTF), the product of the WBSCR9 gene, is invariably deleted in the haploinsufficiency Williams-Beuren Syndrome [31].
• GTF2IRD2 is located in the Williams-Beuren syndrome critical region 7q11.23 and encodes a protein with two TFII-I-like helix-loop-helix repeats [32].
• The association of the Limk1 gene with Williams Syndrome indicates that proteins of this family play a role in the nervous system [33].
• A mouse single-copy gene, Gtf2i, the homolog of human GTF2I, that is duplicated in the Williams-Beuren syndrome deletion region [34].

Analytical, diagnostic and therapeutic context of Williams Syndrome

• Using a gene-targeting approach, we provide evidence that mice with haploinsufficiency for Cyln2 have features reminiscent of Williams syndrome, including mild growth deficiency, brain abnormalities, hippocampal dysfunction and particular deficits in motor coordination [12].
• Detection of hemizygosity at the elastin locus by FISH analysis as a diagnostic test in both classical and atypical cases of Williams syndrome [35].
• We present the case of a patient affected with Williams syndrome (WS), who developed a suspected malignant hyperthermia (MH) reaction to general anesthesia [36].
• Radiation hybrid mapping has shown that this gene is localized 2.33 cR telomeric to D7S1870, a polymorphic marker located at the most telomeric end of the common deletion region of Williams-Beuren syndrome (WBS) [37].
• Comparative genomic sequence analysis of the Williams syndrome region (LIMK1-RFC2) of human chromosome 7q11.23 [38].

References