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Atypical deletion of Williams-Beuren syndrome reveals the mechanism of neurodevelopmental disorders.

ABSTRACT: Genes associated with specific neurocognitive phenotypes in Williams-Beuren syndrome are still controversially discussed. This study identified nine patients with atypical deletions out of 111 patients with Williams-Beuren syndrome; these deletions included seven smaller deletions and two larger deletions. One patient had normal neurodevelopment with a deletion of genes on the distal side of the Williams-Beuren syndrome chromosomal region, including GTF2I and GTF2IRD1. However, another patient retained these genes but showed neurodevelopmental abnormalities. By comparing the genotypes and phenotypes of patients with typical and atypical deletions and previous reports in the literature, we hypothesize that the BAZ1B, FZD9, and STX1A genes may play an important role in the neurodevelopment of patients with WBS.

SUBMITTER: Zhou J

PROVIDER: S-EPMC8981662 | biostudies-literature | 2022 Apr

REPOSITORIES: biostudies-literature

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Atypical deletion of Williams-Beuren syndrome reveals the mechanism of neurodevelopmental disorders.

Zhou Jianrong J Zheng Ying Y Liang Guiying G Xu Xiaoli X Liu Jian J Chen Shaoxian S Ge Tongkai T Wen Pengju P Zhang Yong Y Liu Xiaoqing X Zhuang Jian J Wu Yueheng Y Chen Jimei J

BMC medical genomics 20220404 1

Genes associated with specific neurocognitive phenotypes in Williams-Beuren syndrome are still controversially discussed. This study identified nine patients with atypical deletions out of 111 patients with Williams-Beuren syndrome; these deletions included seven smaller deletions and two larger deletions. One patient had normal neurodevelopment with a deletion of genes on the distal side of the Williams-Beuren syndrome chromosomal region, including GTF2I and GTF2IRD1. However, another patient r ...[more]

PMID: 35379245

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An atypical 7q11.23 deletion in a normal IQ Williams-Beuren syndrome patient.

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Social, neurodevelopmental, endocrine, and head size differences associated with atypical deletions in Williams-Beuren syndrome.

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An atypical 7Q11.2-Q21.11 deletion in a Williams-Beuren syndome patient

Project description: Not available

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Visual phenotype in Williams-Beuren syndrome challenges magnocellular theories explaining human neurodevelopmental visual cortical disorders.

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A 1.3-mb 7q11.23 atypical deletion identified in a cohort of patients with williams-beuren syndrome.

Project description:Williams-Beuren syndrome is a rare multisystem neurodevelopmental disorder caused by a 1.55-1.84-Mb hemizygous deletion on chromosome 7q11.23. The classical phenotype consists of characteristic facial features, supravalvular aortic stenosis, intellectual disability, overfriendliness, and visuospatial impairment. So far, 26-28 genes have been shown to contribute to the multisystem phenotype associated with Williams-Beuren syndrome. Among them, haploinsufficiency of the ELN gene has been shown to cause the cardiovascular anomalies. Identification of patients with atypical deletions has provided valuable information for genotype-phenotype correlation, in which other genes such as LIMK1,CLIP2, GTF2IRD1, or GTF2I have been correlated with specific cognitive profiles or craniofacial features. Here, we report the clinical and molecular characteristics of a patient with an atypical deletion that does not include the GTF2I gene and only partially includes the GTF2IRD1 gene.

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An atypical deletion of the Williams-Beuren syndrome interval implicates genes associated with defective visuospatial processing and autism.

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| S-EPMC2598069 | biostudies-literature

Deletion of the Williams Beuren syndrome critical region unmasks facioscapulohumeral muscular dystrophy.

Project description:Among 1339 unrelated cases accrued by the Italian National Registry for facioscapulohumeral muscular dystrophy (FSHD), we found three unrelated cases who presented signs of Williams-Beuren Syndrome (WBS) in early childhood and later developed FSHD. All three cases carry the molecular defects associated with the two disorders. The rarity of WBS and FSHD, 1 in 7500 and 1 in 20,000 respectively, makes a random association of the two diseases unlikely. These cases open novel and unexpected interpretation of genetic findings. The nonrandom association of both FSHD and WBS points at a gene co-expression network providing hints for the identification of modules and functionally enriched pathways in the two conditions.

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Williams-Beuren syndrome: typical deletions versus atypical deletions of the 7q11.23 region

Project description:We have performed comparative transcriptome profile from lymphoblastoid cell lines from four Williams-Beuren syndrome patients and two patients with partial deletions of the region. The goal was to find deregulated genes specifically in WBS versus atypical deletions, and to determine the biological pathways affected in WBS patients. 6 samples were hybridized twice each: once labeled with Cy5 and once labeled with Cy3 (dye-swap). Each sample was hybridized against a pool of five controls of the same gender.

2010-09-09 | E-GEOD-18188 | biostudies-arrayexpress

Williams-Beuren syndrome: typical deletions versus atypical deletions of the 7q11.23 region

2010-09-09 | GSE18188 | GEO

Autistic disorder in patients with Williams-Beuren syndrome: a reconsideration of the Williams-Beuren syndrome phenotype.

Project description:BACKGROUND: Williams-Beuren syndrome (WBS), a rare developmental disorder caused by deletion of contiguous genes at 7q11.23, has been characterized by strengths in socialization (overfriendliness) and communication (excessive talkativeness). WBS has been often considered as the polar opposite behavioral phenotype to autism. Our objective was to better understand the range of phenotypic expression in WBS and the relationship between WBS and autistic disorder. METHODOLOGY: The study was conducted on 9 French individuals aged from 4 to 37 years old with autistic disorder associated with WBS. Behavioral assessments were performed using Autism Diagnostic Interview-Revised (ADI-R) and Autism Diagnostic Observation Schedule (ADOS) scales. Molecular characterization of the WBS critical region was performed by FISH. FINDINGS: FISH analysis indicated that all 9 patients displayed the common WBS deletion. All 9 patients met ADI-R and ADOS diagnostic criteria for autism, displaying stereotypies and severe impairments in social interaction and communication (including the absence of expressive language). Additionally, patients showed improvement in social communication over time. CONCLUSIONS: The results indicate that comorbid autism and WBS is more frequent than expected and suggest that the common WBS deletion can result in a continuum of social communication impairment, ranging from excessive talkativeness and overfriendliness to absence of verbal language and poor social relationships. Appreciation of the possible co-occurrence of WBS and autism challenges the common view that WBS represents the opposite behavioral phenotype of autism, and might lead to improved recognition of WBS in individuals diagnosed with autism.

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