Genome-Wide Oligonucleotide Array Comparative Genomic Hybridization for Etiological Diagnosis of Mental Retardation

Xiang, Bixia; Zhu, Hongbo; Shen, Yiping; Miller, David T.; Lu, Kangmo; Hu, Xiaofeng; Andersson, Hans; Narumanchi, Tarachandra M.; Wang, Yueying; Martínez, José Enrique; Wu, Bai Lin; Li, Peining; Li, Marilyn M.; Chen, Tian Jian; Fan, Yao Shan

doi:10.2353/jmoldx.2010.090115

Cited by 59 publications

(45 citation statements)

References 29 publications

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“…These results are consistent with a previously published report [19]. Moreover, when Xiang et al [20] studied chromosomal aberrations associated with mental retardation, most of the confirmed pathogenic CNVs were >500 kb in size. In the present study, CNVs >500 kb were more likely to be pathogenic compared with the CNVs that were <500 kb [n = 6/49 (12.2%) vs. n = 1/74 (1.4%); p < 0.05].…”

Section: Resultssupporting

confidence: 82%

Prenatal Diagnosis of DNA Copy Number Variations by Genomic Single-Nucleotide Polymorphism Array in Fetuses with Congenital Heart Defects

Tang

Chen

et al. 2015

Fetal Diagn Ther

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Objectives: To evaluate the usefulness of single-nucleotide polymorphism (SNP) array for prenatal genetic diagnosis of congenital heart defect (CHD), we used this approach to detect clinically significant copy number variants (CNVs) in fetuses with CHDs. Methods: A HumanCytoSNP-12 array was used to detect genomic samples obtained from 39 fetuses that exhibited cardiovascular abnormalities on ultrasound and had a normal karyotype. The relationship between CNVs and CHDs was identified by using genotype-phenotype comparisons and searching of chromosomal databases. All clinically significant CNVs were confirmed by real-time PCR. Results: CNVs were detected in 38/39 (97.4%) fetuses: variants of unknown significance were detected in 2/39 (5.1%), and clinically significant CNVs were identified in 7/39 (17.9%). In 3 of the 7 fetuses with clinically significant CNVs, 3 rare and previously undescribed CNVs were detected, and these CNVs encompassed the CHD candidate genes FLNA (Xq28 dup), BCOR (Xp11.4 dup), and RBL2 (16q12.2 del). Conclusion: Compared with conventional cytogenetic genomics, SNP array analysis provides significantly improved detection of submicroscopic genomic aberrations in pregnancies with CHDs. Based on these results, we propose that genomic SNP array is an effective method which could be used in the prenatal diagnostic test to assist genetic counseling for pregnancies with CHDs.

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Section: Resultssupporting

confidence: 82%

Prenatal Diagnosis of DNA Copy Number Variations by Genomic Single-Nucleotide Polymorphism Array in Fetuses with Congenital Heart Defects

Tang

Chen

et al. 2015

Fetal Diagn Ther

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“…A recent multi-center study on diagnostic aCGH application indicated that 12% of pediatric patients with intellectual disability (ID) and developmental delay (DD) are resulting from chromosomal and genomic imbalances [Xiang et al, 2010]. The recognition of increasing number of pathogenic genomic imbalances facilitates the mapping of dosage-sensitive genes and the understanding of mutagenesis mechanisms [Stankiewicz and Lupski, 2002;Vissers et al, 2010].…”

Section: Discussionmentioning

confidence: 99%

“…Recent diagnostic application of array comparative genomic hybridization (aCGH) for patients with development disorders showed enhanced analytical resolution and improved the abnormality detection rate [Xiang et al, 2008[Xiang et al, , 2010. Increasing number of genomic syndromes resulting from recurrent microdeletions and microduplications mediated by segmental duplicons or low copy repeats have been recognized [Stankiewicz and Lupski, 2002;Vissers et al, 2010].…”

Section: Introductionmentioning

confidence: 99%

A de novo 3.54 Mb deletion of 17q22‐q23.1 associated with hydrocephalus: A case report and review of literature

Khattab

et al. 2011

American J of Med Genetics Pt A

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We describe a female newborn with a de novo 3.54 megabase (Mb) deletion of 17q22-q23.1 (chr17:53,072,536-56,612,662, hg18) including genes from MSI2 to BCAS3 detected by oligonucleotide array comparative genomic hybridization (aCGH). Prenatal ultrasound examination noted oligohydramnios and ventriculomegaly in the fetus. Postnatal examination found hypotonia, macrocephaly, arachnodactyly of fingers and toes, dysmorphic features, bilateral hearing loss and heart defect. Review of reported cases with genomic findings noted one case with proximal deletion involving the NOG gene and a case series with distal recurrent microdeletions involving the TBX2 and TBX4 genes. Our case presented a unique deletion partially overlapped with the above deletions but not including the NOG, TBX2, and TBX4 genes. A genomic map for deletions in this 17q22-q23.1 region was constructed to further define the common deletion intervals for potential haplo-insufficient genes.

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“…McMullan et al, 2009;Xiang et al, 2010;Tucker et al, 2011]. Whereas more than 95% of 'benign' CNVs that occur in healthy subjects have a size !…”

Section: Idiopathic Mental Retardation With or Without Congenital Abnmentioning

confidence: 99%

Genome Arrays for the Detection of Copy Number Variations in Idiopathic Mental Retardation, Idiopathic Generalized Epilepsy and Neuropsychiatric Disorders: Lessons for Diagnostic Workflow and Research

Hochstenbach

Buizer-Voskamp²,

Vorstman

et al. 2011

Cytogenet Genome Res

103

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We review the contributions and limitations of genome-wide array-based identification of copy number variants (CNVs) in the clinical diagnostic evaluation of patients with mental retardation (MR) and other brain-related disorders. In unselected MR referrals a causative genomic gain or loss is detected in 14–18% of cases. Usually, such CNVs arise de novo, are not found in healthy subjects, and have a major impact on the phenotype by altering the dosage of multiple genes. This high diagnostic yield justifies array-based segmental aneuploidy screening as the initial genetic test in these patients. This also pertains to patients with autism (expected yield about 5–10% in nonsyndromic and 10–20% in syndromic patients) and schizophrenia (at least 5% yield). CNV studies in idiopathic generalized epilepsy, attention-deficit hyperactivity disorder, major depressive disorder and Tourette syndrome indicate that patients have, on average, a larger CNV burden as compared to controls. Collectively, the CNV studies suggest that a wide spectrum of disease-susceptibility variants exists, most of which are rare (<0.1%) and of variable and usually small effect. Notwithstanding, a rare CNV can have a major impact on the phenotype. Exome sequencing in MR and autism patients revealed de novo mutations in protein coding genes in 60 and 20% of cases, respectively. Therefore, it is likely that arrays will be supplanted by next-generation sequencing methods as the initial and perhaps ultimate diagnostic tool in patients with brain-related disorders, revealing both CNVs and mutations in a single test.

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Genome-Wide Oligonucleotide Array Comparative Genomic Hybridization for Etiological Diagnosis of Mental Retardation

Cited by 59 publications

References 29 publications

Prenatal Diagnosis of DNA Copy Number Variations by Genomic Single-Nucleotide Polymorphism Array in Fetuses with Congenital Heart Defects

Prenatal Diagnosis of DNA Copy Number Variations by Genomic Single-Nucleotide Polymorphism Array in Fetuses with Congenital Heart Defects

A de novo 3.54 Mb deletion of 17q22‐q23.1 associated with hydrocephalus: A case report and review of literature

Genome Arrays for the Detection of Copy Number Variations in Idiopathic Mental Retardation, Idiopathic Generalized Epilepsy and Neuropsychiatric Disorders: Lessons for Diagnostic Workflow and Research

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