scholarly journals Detection of chromosomal imbalances in children with idiopathic mental retardation by array based comparative genomic hybridisation (array-CGH)

2005 ◽  
Vol 42 (9) ◽  
pp. 699-705 ◽  
Author(s):  
J Schoumans
Keyword(s):  
Mental Retardation ◽  
Array Cgh ◽  
Comparative Genomic Hybridisation ◽  
Comparative Genomic ◽  
Chromosomal Imbalances ◽  
Idiopathic Mental Retardation

scholarly journals Development of a Focused Oligonucleotide-Array Comparative Genomic Hybridization Chip for Clinical Diagnosis of Genomic Imbalance

2007 ◽  
Vol 53 (12) ◽  
pp. 2051-2059 ◽  
Author(s):  
Yiping Shen ◽  
David T Miller ◽  
Sau Wai Cheung ◽  
Va Lip ◽  
Xiaoming Sheng ◽  
...  
Keyword(s):  
Mental Retardation ◽  
Comparative Genomic Hybridization ◽  
Array Comparative Genomic Hybridization ◽  
Developmental Disorders ◽  
Array Cgh ◽  
Clinical Laboratory ◽  
Oligonucleotide Array ◽  
Comparative Genomic ◽  
Genomic Hybridization ◽  
Genomic Imbalance

Abstract Background: Submicroscopic genomic imbalance underlies well-defined microdeletion and microduplication syndromes and contributes to general developmental disorders such as mental retardation and autism. Array comparative genomic hybridization (CGH) complements routine cytogenetic methods such as karyotyping and fluorescence in situ hybridization (FISH) for the detection of genomic imbalance. Oligonucleotide arrays in particular offer advantages in ease of manufacturing, but standard arrays for single-nucleotide polymorphism genotyping or linkage analysis offer variable coverage in clinically relevant regions. We report the design and validation of a focused oligonucleotide-array CGH assay for clinical laboratory diagnosis of genomic imbalance. Methods: We selected >10 000 60-mer oligonucleotide features from Agilent’s eArray probe library to interrogate all subtelomeric and pericentromeric regions and 95 additional clinically relevant regions for a total of 179 loci. Sensitivity and specificity were measured for 105 patient samples, including 51 with known genomic-imbalance events, as detected by bacterial artificial chromosome–based array CGH, FISH, or multiplex ligation-dependent probe amplification. Results: Focused array CGH detected all known regions of genomic imbalance in 51 validation samples with 100% concordance and an excellent signal-to-noise ratio. The mean SD among log2 ratios of all noncontrol features without copy number alteration was 0.062 (median, 0.055). Clinical testing of another 211 samples from individuals with developmental delay, unexplained mental retardation, dysmorphic features, or multiple congenital anomalies revealed genomic imbalance in 25 samples (11.9%). Conclusions: This focused oligonucleotide-array CGH assay, a flexible, robust method for clinically diagnosing genetic disorders associated with genomic imbalance, offers appreciable advantages over currently available platforms.

scholarly journals Cryptic Chromosome Rearrangements in Five Patients, with Normal and/or Abnormal Karyotypes, Associated with Mental Retardation, Autism and/or Epilepsy, Detected by BAC Genome Array-CGH

2012 ◽  
Vol 113 (4) ◽  
pp. 279-288
Author(s):  
V. Cabras ◽  
A. Milia ◽  
C. Montaldo ◽  
Anna Lisa Nucaro
Keyword(s):  
Mental Retardation ◽  
Chromosomal Aberrations ◽  
Reliable Method ◽  
Array Cgh ◽  
Chromosomal Rearrangements ◽  
Phenotype Correlation ◽  
Dysmorphic Features ◽  
Genome Wide ◽  
Genome Array ◽  
Idiopathic Mental Retardation

This report describes the usefulness of the BAC genome array-CGH platform in the detection of cryptic rearrangements. We examined ten patients with normal and/or abnormal karyotypes and dysmorphic features, associated with mental retardation, autism and/or epilepsy. This approach led us to discover further cryptic chromosomal rearrangements, not previously detected by conventional cytogenetic procedures, and allowed us to better delineate genotype/phenotype correlation. Our experience shows the validity of the BAC platform as a reliable method for genome-wide screening of chromosomal aberrations in patient with idiopathic mental retardation and/or in association with autism and epilepsy.

Defining Second-Hit Genetic Abnormalities Involved in the t(12; 21) TEL-AML1 Acute Lymphoblastic Leukemia by Array-Based Comparative Genomic Hybridization.

Blood ◽  
2005 ◽  
Vol 106 (11) ◽  
pp. 2845-2845
Author(s):  
Shinobu Tsuzuki ◽  
Sivasundaram Karnan ◽  
Keizo Horibe ◽  
Kimikazu Matsumoto ◽  
Koji Kato ◽  
...  
Keyword(s):  
Cell Lines ◽  
Gene Fusion ◽  
Array Cgh ◽  
Lymphoblastic Leukemia ◽  
Chimeric Gene ◽  
Clinical Samples ◽  
Comparative Genomic ◽  
Chromosomal Imbalances ◽  
A Genome ◽  
Cycle Regulation

Abstract TEL (ETV6)-AML1 (RUNX1) chimeric gene fusion is the most common genetic abnormality in childhood acute lymphoblastic leukemias (ALL). Evidence suggests that this chimeric gene fusion usually occurs in utero during fetal hematopoiesis and most probably constitutes an initiating or first-hit mutation that is necessary but insufficient for the development of overt, clinical leukemia. In a search for additional secondary and postnatal genetic events that could be linked to leukemia development, we applied a genome- wide array- CGH technique to 24 TEL-AML1 leukemia samples and two cell lines (REH, KOPN41) and found that at least three chromosomal imbalances were involved in all patient samples and cell lines. Recurrent regions of chromosomal imbalances (found in > 10% of clinical samples) were gain of chromosomes 10 (17 %) and 21q (25 %) and loss of chromosomes 2p11 (100 %), 12p13.2 (87 %), 9p21.3 (29 %), 9p13.2 (25 %), 12q21.3, (25 %), 3p21 (21 %), 6q21 (17 %), 4q31.23 (17 %), 11q22-q23 (13 %) and 19q13.11-q13.12 (13 %). The two cell lines showed gain of 21q22.12-qter and loss of 2p11.2, 9p21.3, 12p13.2, and 12q21.3. Among these, six regions of loss (2p11, 3p21, 4q31.23, 9p13.2, 12q21.3 and 19q13.12) have not been identified previously by conventional CGH in TEL-AML1 leukemia. Representative genes involved in the regions of loss were Igkappa (2p11), TEL (12p13.2), p16INK4a/ARF (9p21.3), Pax5 (9p13.2), BTG1 (12q21.3), LIMD1 (3p21), AIM1 and BLIMP1 (6q21), NR3C2 (4q31.23), ATM (11q22-q23), and PDCD5 (19q13.11-q13.12), while the region of gain at 21q contained RUNX1. These findings suggest that, in addition to TEL previously reported as deleted, genes involved in cell cycle regulation, p53 pathways and apoptosis are also often deleted. Our array-CGH obtained data may provide further insights into the molecular basis for the development of TEL-AML1 leukemia.

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