Genome Rearrangements Detected by SNP Microarrays in Individuals with Intellectual Disability Referred with Possible Williams Syndrome

Pani, Ariel M.; Hobart, Holly H.; Morris, Colleen A.; Mervis, Carolyn Β.; Bray‐Ward, Patricia; Kimberley, Kendra W.; Rios, Cecilia; Clark, R. D.; Gulbronson, Maricela D.; Gowans, Gordon C.; Gregg, Ronald G.

doi:10.1371/journal.pone.0012349

Cited by 13 publications

(9 citation statements)

References 51 publications

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“…Epidemiological studies suggest that intellectual disability (ID) affects 2-3% of the general population worldwide and may occur with or without multiple congenital anomalies (MCA) (Rauch et al, 2006;Galasso et al, 2010;Pani et al, 2010;Ropers, 2010).…”

Section: Introductionmentioning

confidence: 99%

Array-CGH analysis in patients with intellectual disability and/or congenital malformations in Brazil

et al. 2016

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ABSTRACT. In several patients, intellectual disability and/or congenital malformation may be attributed to chromosomal changes. In this study, we conducted an array-CGH test of 200 patients from the Northeast of Brazil with intellectual disability and/or congenital malformation. Blood samples were collected from the proband and from their parents when possible. DNA was extracted and investigated using the array-CGH test. Findings were evaluated for the pathogenicity in databases of benign and pathogenic changes (ISCA, UCSC, DGV, and DECIPHER). Forty-seven copy number variations (CNVs) were identified in 43/200 (21.5%) patients, including 25/98 (25.5%) in males and 22/102 (21.57%) in females. We considered 33 of these to be clinically significant, reaching a diagnosis rate of 16.5%. The sizes of the CNVs varied from 102 kb to 24 Mb in deletions and from 115 kb to 140 Mb in duplications. In 10/47 (21.3%) patients, the rearrangement involved a sex chromosome. Thirty-nine patients had one chromosomal aberration, while 2 concomitant abnormalities were detected in 4 patients. Ten of 47 CNVs (21.3%) were > 5Mb in size. Fifteen patients had CNVs related to known syndromes. This research highlights the contribution of submicroscopic chromosomal changes to the etiology of intellectual disability and/or congenital malformation, particularly the implication of chromosomal abnormalities detected using an array-CGH test, with a high rate of 16.5%. Thus, our results support the use of array-CGH replacing standard karyotype as the first-tier cytogenetic diagnostic test for patients with multiple congenital anomalies and/or intellectual disability.

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Section: Introductionmentioning

confidence: 99%

Array-CGH analysis in patients with intellectual disability and/or congenital malformations in Brazil

et al. 2016

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“…Recently, the terminology MD had been replaced with DD/ID referring to patients affected with developmental delay/intellectual disability. Epidemiological data suggests that DD/ID affect up to 3% of the worldwide population and it may concur with or without multiple congenital anomalies (MCA) and also can be found in patients with no phenotypic traits [2] - [4] .…”

Section: Introductionmentioning

confidence: 99%

Screening for Intellectual Disability Using High-Resolution CMA Technology in a Retrospective Cohort from Central Brazil

et al. 2014

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Intellectual disability is a complex, variable, and heterogeneous disorder, representing a disabling condition diagnosed worldwide, and the etiologies are multiple and highly heterogeneous. Microscopic chromosomal abnormalities and well-characterized genetic conditions are the most common causes of intellectual disability. Chromosomal Microarray Analysis analyses have made it possible to identify putatively pathogenic copy number variation that could explain the molecular etiology of intellectual disability. The aim of the current study was to identify possible submicroscopic genomic alterations using a high-density chromosomal microarray in a retrospective cohort of patients with otherwise undiagnosable intellectual disabilities referred by doctors from the public health system in Central Brazil. The CytoScan HD technology was used to detect changes in the genome copy number variation of patients who had intellectual disability and a normal karyotype. The analysis detected 18 CNVs in 60% of patients. Pathogenic CNVs represented about 22%, so it was possible to propose the etiology of intellectual disability for these patients. Likely pathogenic and unknown clinical significance CNVs represented 28% and 50%, respectively. Inherited and de novo CNVs were equally distributed. We report the nature of CNVs in patients from Central Brazil, representing a population not yet screened by microarray technologies.

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“…Genetic experts recommend CMA for screening children with congenital abnormalities, autism spectrum disorders and developmental delays [46, 47]. …”

Section: Emerging Technologiesmentioning

confidence: 99%

Genetic testing: predictive value of genotyping for diagnosis and management of disease

Özgüç

2011

EPMA Journal

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This article describes predictive, preventive value of genetic tests and the implication of the use of testing for personalized treatment. This year marks the 10th anniversity of publishing of the sequence of the human genome. One important area of application of this mega project is a development of genetic tests for mutation detection in single gene disorders that has impact for pediatric age group patients and analyzing susceptibility genes as risk factors in common disorders. Types of genetic tests, new emerging technologies will enable developments of high-throughput approaches by microarrays of great application capacity as described here. As it is usual for all technologies used in health care, bioethical concerns has to be delt with. The ethical, social and governance issues associated with genetic testing are discussed.

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Genome Rearrangements Detected by SNP Microarrays in Individuals with Intellectual Disability Referred with Possible Williams Syndrome

Cited by 13 publications

References 51 publications

Array-CGH analysis in patients with intellectual disability and/or congenital malformations in Brazil

Array-CGH analysis in patients with intellectual disability and/or congenital malformations in Brazil

Screening for Intellectual Disability Using High-Resolution CMA Technology in a Retrospective Cohort from Central Brazil

Genetic testing: predictive value of genotyping for diagnosis and management of disease

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