Dataset Information

Genome rearrangements detected by SNP microarrays in individuals with intellectual disability referred with possible Williams syndrome.

ABSTRACT:

Background

Intellectual disability (ID) affects 2-3% of the population and may occur with or without multiple congenital anomalies (MCA) or other medical conditions. Established genetic syndromes and visible chromosome abnormalities account for a substantial percentage of ID diagnoses, although for approximately 50% the molecular etiology is unknown. Individuals with features suggestive of various syndromes but lacking their associated genetic anomalies pose a formidable clinical challenge. With the advent of microarray techniques, submicroscopic genome alterations not associated with known syndromes are emerging as a significant cause of ID and MCA.

Methodology/principal findings

High-density SNP microarrays were used to determine genome wide copy number in 42 individuals: 7 with confirmed alterations in the WS region but atypical clinical phenotypes, 31 with ID and/or MCA, and 4 controls. One individual from the first group had the most telomeric gene in the WS critical region deleted along with 2 Mb of flanking sequence. A second person had the classic WS deletion and a rearrangement on chromosome 5p within the Cri du Chat syndrome (OMIM:123450) region. Six individuals from the ID/MCA group had large rearrangements (3 deletions, 3 duplications), one of whom had a large inversion associated with a deletion that was not detected by the SNP arrays.

Conclusions/significance

Combining SNP microarray analyses and qPCR allowed us to clone and sequence 21 deletion breakpoints in individuals with atypical deletions in the WS region and/or ID or MCA. Comparison of these breakpoints to databases of genomic variation revealed that 52% occurred in regions harboring structural variants in the general population. For two probands the genomic alterations were flanked by segmental duplications, which frequently mediate recurrent genome rearrangements; these may represent new genomic disorders. While SNP arrays and related technologies can identify potentially pathogenic deletions and duplications, obtaining sequence information from the breakpoints frequently provides additional information.

SUBMITTER: Pani AM

PROVIDER: S-EPMC2930846 | biostudies-literature | 2010 Aug

REPOSITORIES: biostudies-literature

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Publications

Genome rearrangements detected by SNP microarrays in individuals with intellectual disability referred with possible Williams syndrome.

Pani Ariel M AM Hobart Holly H HH Morris Colleen A CA Mervis Carolyn B CB Bray-Ward Patricia P Kimberley Kendra W KW Rios Cecilia M CM Clark Robin C RC Gulbronson Maricela D MD Gowans Gordon C GC Gregg Ronald G RG

PloS one 20100831 8

<h4>Background</h4>Intellectual disability (ID) affects 2-3% of the population and may occur with or without multiple congenital anomalies (MCA) or other medical conditions. Established genetic syndromes and visible chromosome abnormalities account for a substantial percentage of ID diagnoses, although for approximately 50% the molecular etiology is unknown. Individuals with features suggestive of various syndromes but lacking their associated genetic anomalies pose a formidable clinical challen ...[more]

PMID: 20824207

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Project description:Dual-task paradigms can provide insights on the structures and mechanisms underlying information processing and hold diagnostic, prognostic, and rehabilitative value for populations with cognitive deficits such as in individuals with intellectual disability (ID). In this paradigm, two tasks are performed separately (single-task context) and concurrently (dual-task context). The change in performance from single- to dual-task context represents dual-task interference. Findings from dual-task studies have been largely inconsistent on whether individuals with ID present with dual-task-specific deficits. The current review aimed to map the published literature on dual-task methods and pattern of dual-task interference in individuals with ID. A scoping review based on Arksey and O'Malley's five-stage methodological framework was performed. Seventeen electronic databases and registries were searched to identify relevant studies, including gray literature. Charted data from included studies were analyzed quantitatively and qualitatively. PRISMA guidelines informed the reporting of this review. Twenty-two studies involving 1,102 participants (656 with ID and 446 without ID) met the review's inclusion criteria. Participants in the included studies were heterogeneous in sex, age (range 3-59 years), etiology and ID severity. Included studies characterized their ID-sample in different ways, most commonly using intelligence quotient (IQ) scores. Other measures of intellectual function (e.g., mental age, ID severity, verbal and/or visuospatial ability scores) were also used, either solely or in combination with IQ. Methods of dual-task testing varied across studies, particularly in relation to dual-task combinations, equation of single-task performance between groups, measurement and reporting of dual-task performance for each single-task, and task priority instructions. Thematic content of the included studies were: (1) structural interference to dual-tasking; (2) etiology-based differences in dual-tasking; (3) gait and balance dual-task performance; (4) testing executive function using dual-task paradigms; and (5) training effect on dual-task performance. Although the evidence consistently supported the intact dual-tasking ability of individuals with ID, the pattern of dual-task interference was inconsistent. Likewise, the evidence was inconclusive regarding dual-task deficit specific to individuals with ID because of heterogeneity in dual-task study designs among included studies.

Dataset Information

Genome rearrangements detected by SNP microarrays in individuals with intellectual disability referred with possible Williams syndrome.

Background

Methodology/principal findings

Conclusions/significance

Publications

Genome rearrangements detected by SNP microarrays in individuals with intellectual disability referred with possible Williams syndrome.

Similar Datasets

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