Comparative genomic hybridisation in mentally retarded patients with dysmorphic features and a normal karyotype

2001 ◽  
Vol 60 (3) ◽  
pp. 212-219 ◽  
Author(s):  
G Joly ◽  
J-M Lapierre ◽  
C Ozilou ◽  
P Gosset ◽  
A Aurias ◽  
...  
Keyword(s):  
Normal Karyotype ◽  
Mentally Retarded ◽  
Comparative Genomic Hybridisation ◽  
Comparative Genomic ◽  
Dysmorphic Features

High-Resolution Genomic Profiling of Myelodysplasia (MDS) by Microarray Comparative Genomic Hybridization (CGH).

Blood ◽  
2006 ◽  
Vol 108 (11) ◽  
pp. 2645-2645
Author(s):  
Noor Esoof ◽  
Aristoteles Giagounidis ◽  
Mario Cazzola ◽  
Luca Malcovati ◽  
Carlo Aul ◽  
...  
Keyword(s):  
Copy Number ◽  
Genomic Dna ◽  
Normal Karyotype ◽  
Comparative Genomic Hybridisation ◽  
Comparative Genomic ◽  
Bac Clones ◽  
Conventional Cytogenetic Analysis ◽  
Copy Number Changes ◽  
Normal Controls ◽  
Microarray Cgh

Abstract Myelodysplasia (MDS) is a heterogeneous group of clonal disorders of hematopoietic stem cells characterised by ineffective hematopoiesis and a variable risk of transformation to acute myelogenous leukaemia. We have used Comparative Genomic Hybridisation (CGH) microarray analysis, a technology that represents a significant improvement in resolution over conventional cytogenetic analysis, to screen genomic DNA from MDS patients for the identification of genome-wide Copy-Number Changes (CNCs). We have studied genomic DNA obtained from the neutrophil population of 48 MDS patients and 40 normal controls. Of the 48 MDS patients 10 had the 5q- syndrome, 32 were assigned normal karyotype and 6 had complex karyotypes. Comparative Genomic Hybridisation (CGH) microarray analysis was performed using microarrays containing 3500 BAC clones at 1Mb intervals over the whole human genome. Furthermore we used a whole genome tiling-path (27 000 overlapping BAC clones) array to profile 9 5q-syndrome patients and for 3 of those patients the T-cell DNA were also profiled to act as constitutional control. The patient DNA and a pool of normal reference DNA was labelled with different fluorochromes and cohybridised to the microarray. The normalised ratio of signal intensities was calculated and log2 ratios between −0.4 and 0.4 were considered normal. Ratios below or above the normal range were interpreted as loss or gain of genetic material, respectively. The deletions on chromosome 5q were precisely mapped by array-CGH in the patients with the 5q- syndrome but no additional CNCs were detected. One of the 5q deletions, however, displayed a discontiguous pattern with the tiling resolution array. Copy-number changes (CNCs) that escaped conventional cytogenetic detection were identified in the MDS patients originally reported with normal bone marrow karyotypes. 8 out of those 32 patients displayed CNCs that were not detected in the 40 normal controls and as such were considered as disease-related changes (non-polymorphic). Many of those CNCs were single-clone abberrations that were validated by dye-swap experiments and some were confirmed by quantitative PCR. Microarray CGH data confirmed all abnormalities reported by conventional cytogenetic analysis in the MDS patients with complex karyotypes and previously undetected abnormalities were uncovered. Several genes involved in either the initiation or progression of hematological malignancies are known to map within the cryptic abnormalities identified in the patients studied. For example, one patient with an apparently normal karyotype showed a small deletion at 17q11 which encompasses the NF1 gene. Further work will determine whether particular abnormalities detected by microarray CGH are recurrent and the nature of the genes involved. However, the promise of microarray CGH in the diagnostic work up of MDS particularly in those patients with normal karyotypes is clear.

scholarly journals Comprehensive Genetic Evaluation of Children With Syndromic Craniosynostosis by a Combination of Cytogenetics, Multiplex Ligation-dependent Probe Amplification and Array-based Comparative Genomic Hybridisation

2021 ◽  
Author(s):  
Trayan Nedyalkov Delchev ◽  
Savina Hadjidekova ◽  
Hadil Kathom ◽  
Stoyan Bichev ◽  
Tsvetina Veleva ◽  
...  
Keyword(s):  
Chromosomal Rearrangements ◽  
Clinical Manifestations ◽  
Normal Karyotype ◽  
Medical Problem ◽  
Genetic Evaluation ◽  
Comparative Genomic Hybridisation ◽  
Comparative Genomic ◽  
Pathological Findings ◽  
Syndromic Craniosynostosis ◽  
Dependent Probe

Abstract Syndromic craniosynostosis (SC) is a genetically determined premature closure of one or more of the cranial sutures, which may result in severe dysmorphism, increased intracranial pressure along with many other clinical manifestations. The considerable risk of complications along with significant incidence makes these cranial deformations an important medical problem. Despite the efforts to clarify the pathogenesis of SC in recent years, its genetic aspects remain largely unknown.Aiming to elucidate the complex genetic etiology of syndromic craniosynostosis, we conducted an investigation of 39 children, screened systematically with a combination of conventional cytogenetic analysis, multiplex ligation-dependent probe amplification (MLPA) and array-based comparative genomic hybridisation (aCGH).Pathological findings were established in 15.3% (6/39) of the cases using aCGH, in 7.7% (3/39) using MLPA and 2.5% (1/39) using conventional karyotyping. About 12.8% (5/39) of the patients with normal karyotype carried submicroscopic chromosomal rearrangements. Duplications were found to be more common than deletions.Conclusion: The systematic genetic evaluation of children with SC revealed a high prevalence of submicrosopic chromosomal rearrangements (most commonly duplications and gain-of-function variations). This suggests the leading role of those defects in the pathogenesis of syndromic craniosynostosis. The genetic complexity of SC was reaffirmed by the discovery of pathological findings in various chromosomal regions. Certain genes were discussed in conjunction with craniosynostosis.

De novo monosomy 9p24.3-pter and trisomy 17q24.3-qter characterised by microarray comparative genomic hybridisation in a fetus with an increased nuchal translucency

2006 ◽  
Vol 26 (3) ◽  
pp. 206-213 ◽  
Author(s):  
Sophie Brisset ◽  
Serdar Kasakyan ◽  
Aurore Coulomb L'Herminé ◽  
Valérie Mairovitz ◽  
Evelyne Gautier ◽  
...  
Keyword(s):  
De Novo ◽  
Nuchal Translucency ◽  
Comparative Genomic Hybridisation ◽  
Comparative Genomic ◽  
Increased Nuchal Translucency

P–575 Patients with recurrent implantation failures (RIF): chromosome abnormalities in the resulting embryos

2021 ◽  
Vol 36 (Supplement_1) ◽  
Author(s):  
C Albanese ◽  
D Perruzza ◽  
C Tabanelli ◽  
S Sgargi ◽  
M C Magli ◽  
...  
Keyword(s):  
Live Birth ◽  
Uterine Cavity ◽  
Implantation Rate ◽  
Normal Karyotype ◽  
Great Majority ◽  
Chromosome Analysis ◽  
Delivery Rate ◽  
Comparative Genomic ◽  
Male Factor ◽  
Preimplantation Genetic Testing

Abstract Study question Do RIF patients have the preimplantation genetic testing for aneuploidy (PGT-A) overcome their infertility condition? Summary answer PGT-A positively impact on implantation rate in RIF patients What is known already The most common definition of RIF is failure to achieve a pregnancy after three consecutive transfers of good quality embryos. This term possibly represents a heterogeneous category of infertile couples as the causes of repeated failures can be diverse. Especially intriguing is the case of patients with an age lower than 39 years for which the oocyte quality is expected not to be compromised by the well known age effect on female fertility. The chromosome analysis of the resulting embryos has been proposed as a valid method to improve implantation in the great majority of RIF patients Study design, size, duration This retrospective study included 49 patients with at least three previous consecutive implantation failures, which underwent PGT-A from January 2016 to April 2020. Both partners had a normal karyotype. Only patients with a female age below 39 years were included, who presented with a normal uterine cavity. Couples with a severe male factor were excluded. Single frozen blastocysts were transferred according to chromosomal results Participants/materials, setting, methods Maternal age was 35.5 ± 3.1 years. All blastocysts were vitrified after trophectoderm biopsy. Whole genome amplification and array comparative genomic hybridization were performed on biopsies. Only euploid embryos were transferred. The primary outcome was the live-birth delivery rate after the first transfer Main results and the role of chance Before starting a PGT-A cycle, these patients underwent 213 embryo transfers with 251 embryos replaced. A total of 264 blastocysts were analyzed, 140 of which were aneuploid (53%). Monosomy or trisomy was reported in 67 of the diagnosed samples (67/140, 48%) whereas the remaining 73 carried complex aneuploidies (73/140, 52%). The remaining 124 blastocysts (47%) were diagnosed as euploid. All patients performed an embryo transfer resulting in 28 clinical pregnancies (57%). There were 5 spontaneous abortions and the live-birth delivery rate per patient was 47% Limitations, reasons for caution This study suffers from the weakness related to retrospectivity. In addition, as euploid embryos are still cryopreserved, the delivery rate could change at completion of the cycles Wider implications of the findings: A RIF condition can be attributed, at least in a good proportion of cases, to the generation of high percentages of aneuploid embryos. In this case, the transfer of euploid blastocysts has high chances to classify this category of RIF patients has having an embryonic cause of infertilit. Trial registration number Not applicable

Development of a genomic predictive model for cholangiocarcinoma using copy number alteration data

2021 ◽  
pp. jclinpath-2020-207346
Author(s):  
Inês Tavares ◽  
Ricardo Martins ◽  
Ilda Patrícia Ribeiro ◽  
Luísa Esteves ◽  
Francisco Caramelo ◽  
...  
Keyword(s):  
Survival Analysis ◽  
Copy Number ◽  
Patient Management ◽  
Copy Number Alteration ◽  
Comparative Genomic Hybridisation ◽  
Support Vector ◽  
Comparative Genomic ◽  
Support Vector Machine Algorithm ◽  
Rare Tumour ◽  
Genomic Model

AimsCholangiocarcinoma (CC) is a rare tumour arising from the biliary tract epithelium. The aim of this study was to perform a genomic characterisation of CC tumours and to implement a model to differentiate extrahepatic (ECC) and intrahepatic (ICC) cholangiocarcinoma.MethodsDNA extracted from tumour samples of 23 patients with CC, namely 10 patients with ECC and 13 patients with ICC, was analysed by array comparative genomic hybridisation. A support vector machine algorithm for classification was applied to the genomic data to distinguish between ICC and ECC. A survival analysis comparing both groups of patients was also performed.ResultsWith these whole genome results, we observed several common alterations between tumour samples of the same CC anatomical type, namely gain of Xp and loss of 3p, 11q11, 14q, 16q, Yp and Yq in ICC tumours, and gain of 16p25.3 and loss of 3q26.1, 6p25.3–22.3, 12p13.31, 17p, 18q and Yp in ECC tumours. Gain of 2q37.3 was observed in the samples of both tumour subtypes, ICC and ECC. The developed genomic model comprised four chromosomal regions that seem to enable the distinction between ICC and ECC, with an accuracy of 71.43% (95% CI 43% to 100%). Survival analysis revealed that in our cohort, patients with ECC survived on average 8 months less than patients with ICC.ConclusionsThis genomic characterisation and the introduction of genomic models to clinical practice could be important for patient management and for the development of targeted therapies. The power of this genomic model should be evaluated in other CC populations.

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