Epileptic Seizures Associated with Chromosomal Abnormalities Detected by Array Comparative Genomic Hybridization in Five Albanian Children

2017 ◽  
Vol 06 (03) ◽  
pp. 156-160
Author(s):  
Anila Babameto-Laku ◽  
Serla Grabova ◽  
Jera Kruja ◽  
Gentian Vyshka
Keyword(s):  
Intellectual Disability ◽  
Comparative Genomic Hybridization ◽  
Diagnostic Tool ◽  
Array Cgh ◽  
Chromosomal Abnormalities ◽  
Case Reports ◽  
Epileptic Seizures ◽  
Comparative Genomic ◽  
Genomic Hybridization ◽  
Novel Technologies

AbstractEpilepsy is an ever-changing field of research, with genetics and genomics playing a very important role in recent times. Novel technologies detecting chromosomal aberrations are applied widely, and array-based comparative genomic hybridization (array CGH) has become a basic diagnostic tool in a variety of neurologic and neuropsychiatric conditions. The authors describe five Albanian children suffering from epilepsy and screened for genetic problems using array CGH and other methods. A thorough neurological examination and imaging studies were performed for all patients, who in addition to seizures, suffered from diverse medical conditions such as microcephaly, developmental delay, intellectual disability, dysmorphic features, heart anomalies, cryptorchidism, and other clinical stigmata of an aberrant neurodevelopment. It is evident from our case reports that the array CGH as a diagnostic tool in molecular genetics has facilitated the recognition of microdeletions and microduplications as risk factors for both generalized and focal epilepsies. This method, therefore, clearly has a practical and scientific value in the investigation of children with epilepsy and associated intellectual disability and congenital anomalies.

scholarly journals Application of Microarray-Based Comparative Genomic Hybridization in Prenatal and Postnatal Settings: Three Case Reports

2011 ◽  
Vol 2011 ◽  
pp. 1-9
Author(s):  
Jing Liu ◽  
Francois Bernier ◽  
Julie Lauzon ◽  
R. Brian Lowry ◽  
Judy Chernos
Keyword(s):  
Comparative Genomic Hybridization ◽  
Array Cgh ◽  
Case Reports ◽  
Copy Number Variations ◽  
Diagnostic Process ◽  
Comparative Genomic ◽  
Complex Nature ◽  
Genomic Hybridization ◽  
Entire Genome ◽  
Efficient Detection

Microarray-based comparative genomic hybridization (array CGH) is a newly emerged molecular cytogenetic technique for rapid evaluation of the entire genome with sub-megabase resolution. It allows for the comprehensive investigation of thousands and millions of genomic loci at once and therefore enables the efficient detection of DNA copy number variations (a.k.a, cryptic genomic imbalances). The development and the clinical application of array CGH have revolutionized the diagnostic process in patients and has provided a clue to many unidentified or unexplained diseases which are suspected to have a genetic cause. In this paper, we present three clinical cases in both prenatal and postnatal settings. Among all, array CGH played a major discovery role to reveal the cryptic and/or complex nature of chromosome arrangements. By identifying the genetic causes responsible for the clinical observation in patients, array CGH has provided accurate diagnosis and appropriate clinical management in a timely and efficient manner.

scholarly journals Novel Chromosomal Abnormalities Identified by Comparative Genomic Hybridization in Parathyroid Adenomas1

1998 ◽  
Vol 83 (5) ◽  
pp. 1766-1770 ◽  
Author(s):  
Nallasivam Palanisamy ◽  
Yasuo Imanishi ◽  
Pulivarthi H. Rao ◽  
Hideki Tahara ◽  
R. S. K. Chaganti ◽  
...  
Keyword(s):  
Tumor Suppressor ◽  
Comparative Genomic Hybridization ◽  
Tumor Suppressor Genes ◽  
Chromosomal Abnormalities ◽  
Suppressor Gene ◽  
Comparative Genomic ◽  
Parathyroid Tumor ◽  
Genomic Hybridization ◽  
Suppressor Genes ◽  
Parathyroid Adenomas

The molecular basis of parathyroid adenomatosis includes defects in the cyclin D1/PRAD1 and MEN1 genes but is, in large part, unknown. To identify new locations of parathyroid oncogenes or tumor suppressor genes, and to further establish the importance of DNA losses described by molecular allelotyping, we performed comparative genomic hybridization (CGH) on a panel of 53 typical sporadic (nonfamilial) parathyroid adenomas. CGH is a new molecular cytogenetic technique in which the entire tumor genome is screened for chromosomal gains and/or losses. Two abnormalities, not previously described, were found recurrently: gain of chromosome 16p (6 of 53 tumors, or 11%) and gain of chromosome 19p (5 of 53, or 9%). Losses were found frequently on 11p (14 of 53, or 26%), as well as 11q (18 of 53, or 34%). Recurrent losses were also seen on chromosomes 1p, 1q, 6q, 9p, 9q, 13q, and 15q, with frequencies ranging from 8–19%. Twenty-four of the 53 adenomas were also extensively analyzed with polymorphic microsatellite markers for allelic losses, either in this study (11 cases) or previously (13 cases). Molecular allelotyping results were highly concordant with CGH results in these tumors (concordance level of 97.5% for all informative markers/chromosome arms examined). In conclusion, CGH has identified the first two known chromosomal gain defects in parathyroid adenomas, suggesting the existence of direct-acting parathyroid oncogenes on chromosomes 16 and 19. CGH has confirmed the locations of putative parathyroid tumor suppressor genes, also defined by molecular allelotyping, on chromosomes 1p, 6q, 9p, 11q, 13q, and 15q. Finally, CGH has provided new evidence favoring the possibility that distinct parathyroid tumor suppressors exist on 1p and 1q, and has raised the possibility of a parathyroid tumor suppressor gene on 11p, distinct from the MEN1 gene on 11q. CGH can identify recurrent genetic abnormalities in hyperparathyroidism, especially chromosomal gains, that other methods do not detect.

scholarly journals Subtelomeric Rearrangements: Presentation of 21 Probands with Emphasis on Familial Cases

2019 ◽  
Vol 32 (7-8) ◽  
pp. 529
Author(s):  
Ana Rita Soares ◽  
Gabriela Soares ◽  
Manuela Mota-Freitas ◽  
Natália Oliva-Teles ◽  
Ana Maria Fortuna
Keyword(s):  
Intellectual Disability ◽  
Comparative Genomic Hybridization ◽  
Chromosomal Abnormality ◽  
Array Comparative Genomic Hybridization ◽  
De Novo ◽  
Family Members ◽  
Comparative Genomic ◽  
Genomic Hybridization ◽  
Subtelomeric Rearrangements

Introduction: Intellectual disability affects 2% – 3% of the general population, with a chromosomal abnormality being found in 4% – 28% of these patients and a cryptic subtelomeric abnormality in 3% – 16%. In most cases, these subtelomeric rearrangements are submicroscopic, requiring techniques other than conventional karyotype for detection. They may be de novo or inherited from an affected parent or from a healthy carrier of a balanced chromosomal abnormality. The aim of this study was to characterize patients from our medical genetics center, in whom both a deletion and duplication in subtelomeric regions were found.Material and Methods: Clinical and cytogenetic characterization of 21 probands followed at our center, from 1998 until 2017, with subtelomeric rearrangements.Results: There were 21 probands from 19 families presenting with intellectual disability and facial dysmorphisms. Seven had behavior changes, five had epilepsy and 14 presented with some other sign or symptom. Four had chromosomal abnormalities detected by conventional karyotype and four were diagnosed by array-comparative genomic hybridization. In four cases, parental studies were not possible. The online mendelian inheritance in man classification was provided whenever any of the phenotypes (deletion or duplication syndrome) was dominant.Discussion: Patients and relevant family members were clinically and cytogenetically characterized. Although rare, subtelomeric changes are a substantial cause of syndromic intellectual disability with important familial repercussions. It is essential to remember that a normal array-comparative genomic hybridization result does not exclude a balanced rearrangement in the parents.Conclusion: Parental genetic studies are essential not only for a complete characterization of the rearrangement, but also for accurate genetic counselling and screening of family members at risk for recurrence.

Intellectual disability; an example of not relying on karyotype or array comparative genomic hybridization alone

Meta Gene ◽  
2020 ◽  
Vol 24 ◽  
pp. 100666
Author(s):  
Farhad Khadivi zand ◽  
Mohammad Shariati ◽  
Amirsaeed Sabeti Aghabozorgi ◽  
Sohelia Saberi ◽  
Haniyeh Khatib Astaneh ◽  
...  
Keyword(s):  
Intellectual Disability ◽  
Comparative Genomic Hybridization ◽  
Array Comparative Genomic Hybridization ◽  
Comparative Genomic ◽  
Genomic Hybridization

Clinical Utility of Array Comparative Genomic Hybridization for Detection of Chromosomal Abnormalities in Pediatric Acute Lymphoblastic Leukemia.

Blood ◽  
2006 ◽  
Vol 108 (11) ◽  
pp. 2275-2275
Author(s):  
Karen Rabin ◽  
Chris Man ◽  
Sharon Plon ◽  
Pulivarthi Rao ◽  
Rizwan Naeem
Keyword(s):  
Comparative Genomic Hybridization ◽  
Clinical Utility ◽  
Array Comparative Genomic Hybridization ◽  
Array Cgh ◽  
Lymphoblastic Leukemia ◽  
Comparative Genomic ◽  
Genomic Hybridization ◽  
Structural Abnormalities ◽  
Pediatric All ◽  
Balanced Translocations

Abstract Chromosomal structural abnormalities in ALL are powerful independent predictors of prognosis, and directly impact choice of therapy. Currently, clinical detection of these abnormalities is based on karyotype and fluorescent in-situ hybridization (FISH), but these methods have limitations. Under optimal circumstances, structural abnormalities are detectable in well over 90% of ALL cases, but in actuality, typical cytogenetic laboratories demonstrate only a 50–60% abnormality detection rate. Karyotype may fail due to unsuccessful cell growth in culture and/or relative overgrowth of normal lymphocytes. FISH is limited by the expense and labor intensity of performing a separate assay for each probe used. Array comparative genomic hybridization (CGH) may have clinical utility as a complementary diagnostic tool in pediatric ALL. Its advantages include the ability to detect copy number changes in regions too small to be identifiable by karyotype; to identify novel abnormalities for which specific FISH probes do not exist in current diagnostic laboratories; and to provide information in as many as 50% of cases which show a failed or normal karyotype. In addition to its clinical utility, array CGH provides a wealth of information which may be mined for discovery of new pathways in leukemogenesis and additional prognostic factors within existing disease subgroups. The main limitation of array CGH is its inability to detected balanced translocations. We evaluated the diagnostic utility of a bacterial artificial chromosome (BAC) array CGH platform, the SpectralChip 2600, with an average resolution of 1.0 MB across the genome. We analyzed 50 pediatric ALL bone marrow specimens obtained at diagnosis, and compared the findings to the clinical results based on karyotype and standard 5-probe FISH panel. The cases ranged from 1–15 years (mean 5 years), with marrow containing between 33–94% leukemic blasts (mean 77%). Each sample was hybridized to the chip with a healthy control of the opposite gender. The sensitivity of array CGH in detecting abnormalities identified by karyotype and FISH was approximately 88%. Several of the abnormalities “missed” by CGH, which lowered the sensitivity score, were subsequently found to be erroneous karyotype calls when followed up with specific FISH probes. In addition, array CGH detected numerous additional areas of amplification and deletion which were subsequently validated by FISH, including in 10 cases for which cytogenetics was either normal or unsuccessful. Loss of 1p31, loss of 7p21, and gain of 16p13 were aberrations that were each noted to occur in three or more different cases, and hence may be worthy of further study. In the future, development of a customized ALL chip which is enriched for probes at sites of known amplification and deletion could further heighten diagnostic sensitivity, obviate the need for performance of multiple FISH tests, and provide valuable information in the substantial number of cases with a normal or failed karyotype analysis. Balanced translocations would still require testing via a multiplex PCR assay or a combination of available FISH probes.

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