Identification of modifying copy number variations in healthy carriers of pathogenetically significant CNVs

2021 ◽  
pp. 47-49
Author(s):  
Е.О. Беляева ◽  
А.А. Кашеварова ◽  
С.А. Васильев ◽  
Н.А. Скрябин ◽  
М.Е. Лопаткина ◽  
...  
Keyword(s):  
Genetic Counseling ◽  
Copy Number ◽  
Asymptomatic Carrier ◽  
Phenotypic Variability ◽  
Copy Number Variations ◽  
Fundamental Importance ◽  
Modifying Effect ◽  
Chromosomal Variants ◽  
Healthy Carriers

Присутствие дополнительных хромосомных вариантов в геноме пациента или бессимптомное носительство аберрации может приводить к фенотипической вариабельности проявлений патогенетически значимой CNV. Высказана гипотеза, что сочетанное действие CNV оказывает модифицирующий эффект, который может быть кумулятивным или компенсаторным, и, соответственно, изменять риск, связанный с определённой CNV, что имеет принципиальное значение для медико-генетического консультирования. The presence of concomitant chromosomal variants in the genome of a patient or an asymptomatic carrier of aberrations may lead to phenotypic variability of pathogenetically significant CNV. It is supposed, that multiple CNVs has a modifying effect, which can be cumulative or compensatory. The risk associated with a particular CNV changes accordingly. This is of fundamental importance for genetic counseling.

scholarly journals Prenatal diagnosis of 2q13 duplications: The crucial role of the family survey in genetic counseling on novel copy number variations

2020 ◽  
Vol 63 (8) ◽  
pp. 103956
Author(s):  
Hela Bellil ◽  
Denise Molina-Gomes ◽  
Thibaud Quibel ◽  
Sophie Roy ◽  
Rodolphe Dard ◽  
...  
Keyword(s):  
Genetic Counseling ◽  
Prenatal Diagnosis ◽  
Crucial Role ◽  
Copy Number ◽  
Copy Number Variations ◽  
The Family

scholarly journals Copy number variations of chromosome 17p11.2 region in children with development delay and in fetuses with abnormal imaging findings

2021 ◽  
Author(s):  
Yuanyuan Zhang ◽  
Xiaoliang Liu ◽  
Haiming Gao ◽  
Rong He ◽  
Guoming Chu ◽  
...  
Keyword(s):  
Copy Number ◽  
Phenotypic Variability ◽  
Copy Number Variations ◽  
Congenital Defects ◽  
Genetic Characteristics ◽  
Development Delay ◽  
Chromosome Imbalance ◽  
Next Generation Sequencing Ngs ◽  
Generation Sequencing ◽  
Dependent Probe

Abstract Background: Deletion and duplication of the -3.7 Mb region in 17p11.2 result in two reciprocal syndromes, Smith-Magenis syndrome and Potocki-Lupski syndrome, which are well-known development disorders. The purpose of this study is to identify the prevalence, genetic characteristics and clinical phenotype of 17p11.2 deletion/duplication in Chinese children with development delay and in fetuses with potential congenital defects.Methods: 7077 children with development delay and/or intellectual disability were screened by multiplex ligation-dependent probe amplification (MLPA) P245 assay. 7319 fetuses with potential congenital defects were detected using next generation sequencing (NGS) technique.Results: 417 of 7077 children patients were identified to carry chromosome imbalance. Among them, 28 (28/7077, 0.4 %) cases had imbalance at chromosome 17p11.2, of which 12 cases (42.9 %) had heterozygous deletions and 16 (57.1 %) had heterogeneous duplications. The phenotypes of these 28 children were variable, including neurobehavioral disorders, craniofacial/skeletal anomalies, immunologic defects, ocular problems, and organ malformations. 263 of 7319 fetuses were recognized to have genomic copy number variations (CNV). Only 2 of them were found to harbor 17p11.2 imbalance. The fetus with deletion presented with ventricular septal defect and the fetus with reciprocal duplication had cerebral ventricle dilation.Conclusion: Our study highlights the phenotypic variability associated with 17p11.2 variations in China. The results further expand the phenotypic spectrum of SMS/PTLS and increase awareness of these disruptive mutations among clinicians.

Clinical Implications of Chromosome 16 Copy Number Variation

2021 ◽  
pp. 1-9
Author(s):  
Emine Ikbal Atli ◽  
Sinem Yalcintepe ◽  
Engin Atli ◽  
Selma Demir ◽  
Cisem Mail ◽  
...  
Keyword(s):  
Copy Number ◽  
Clinical Presentation ◽  
Phenotypic Variability ◽  
Copy Number Variations ◽  
Comparative Genomic Hybridisation ◽  
Comparative Genomic ◽  
Chromosome 16 ◽  
Genomic Changes ◽  
Number Variation ◽  
Nonallelic Homologous Recombination

Chromosome 16 is one of the gene-rich chromosomes; however, approximately 10% of the chromosome 16 sequence is composed of segmental copies, which renders this chromosome instable and predisposes it to rearrangements via frequent nonallelic homologous recombination. Microarray technologies have enabled the analysis of copy number variations (CNV), which may be associated with the risk of developing complex diseases. Through comparative genomic hybridisation in 1,298 patients, we detected 18 cases with chromosome 16 CNV. We identified 2recurrent CNV regions, including 1 at 16p13.11 in 4 patients and another at 16p11.2 in 7 patients. We also detected atypical chromosome 16 rearrangements in 7 patients. Furthermore, we noted an increased frequency of co-occurring genomic changes, supporting the two-hit hypothesis to explain the phenotypic variability in the clinical presentation of CNV syndromes. Our findings can contribute to the creation of a chromosome 16 disease map based on regions that may be associated with disease development.

scholarly journals Relevance of Copy Number Variation at Chromosome X in Male Fetuses Inherited from the Mother May Be Ascertained by Including Male Relatives from the Maternal Lineage in Addition to Trio Analyses

Genes ◽  
2020 ◽  
Vol 11 (9) ◽  
pp. 979
Author(s):  
Ming Chen ◽  
Wan-Ju Wu ◽  
Mei-Hui Lee ◽  
Tien-Hsiung Ku ◽  
Gwo-Chin Ma
Keyword(s):  
Genetic Counseling ◽  
Copy Number ◽  
Copy Number Variations ◽  
Chromosome X ◽  
Genetic Changes ◽  
Monogenic Disorders ◽  
Variants Of Unknown Significance ◽  
Unknown Significance ◽  
Number Variation ◽  
Extended Analysis

Chromosome microarray analysis has been used for prenatal detection of copy number variations (CNVs) and genetic counseling of CNVs has been greatly improved after the accumulation of knowledge from postnatal outcomes in terms of the genotype-phenotype correlation. However, a significant number of CNVs are still regarded as variants of unknown significance (VUS). CNVs at the chromosome X (X-CNVs) represent a unique group of genetic changes in genetic counseling; X-CNVs are similar to X-linked recessive monogenic disorders in that the prognosis in males is expected to be poor. Trio analysis is typically advised to patients with X-CNVs but such an approach may be inadequate in prenatal settings since the clinical relevance is sometimes uninformative, particularly for the maternally inherited X-CNVs in male fetuses. Here, we reported four healthy women whose male fetuses were found to have X-CNVs inherited from the mothers. The X-CNVs were initially recognized as VUS or likely pathogenic in males according to the publicly available information. After extending genetic analyses to male relatives of the maternal lineages, however, the relevance of the X-CNVs was reconsidered to be likely benign. The results highlight that an extended analysis to include more relatives, in addition to the parents, provides further information for genetic counseling when X-CNVs are encountered in prenatal settings.

scholarly journals Copy number variations of chromosome 17p11.2 region in children with development delay and in fetuses with abnormal imaging findings

2021 ◽  
Vol 14 (1) ◽  
Author(s):  
Yuanyuan Zhang ◽  
Xiaoliang Liu ◽  
Haiming Gao ◽  
Rong He ◽  
Guoming Chu ◽  
...  
Keyword(s):  
Copy Number ◽  
Phenotypic Variability ◽  
Copy Number Variations ◽  
Congenital Defects ◽  
Genetic Characteristics ◽  
Clinical Phenotypes ◽  
Development Delay ◽  
Chromosome Imbalance ◽  
Generation Sequencing ◽  
Dependent Probe

Abstract Background Deletion and duplication of the 3.7 Mb region in 17p11.2 result in two syndromes, Smith-Magenis syndrome and Potocki-Lupski syndrome, which are well-known development disorders. The purpose of this study was to determine the prevalence, genetic characteristics and clinical phenotypes of 17p11.2 deletion/duplication in Chinese children with development delay and in fetuses with potential congenital defects. Methods 7077 children with development delay and/or intellectual disability were screened by multiplex ligation-dependent probe amplification P245 assay. 7319 fetuses with potential congenital defects were tested using next generation sequencing technique. Results 417 of 7077 pediatric patients were determined to carry chromosome imbalance. 28 (28/7077, 0.4%) cases had imbalance at chromosome 17p11.2. Among them, 12 cases (42.9%) had heterozygous deletions and 16 cases (57.1%) had heterozygous duplications. The clinical phenotypes were variable, including neurobehavioral disorders, craniofacial/skeletal anomalies, immunologic defects, ocular problems and organ malformations. 263 of 7319 fetuses were recognized to have genomic copy number variations. Only 2 of them were found to harbor 17p11.2 imbalance. The fetus with deletion presented with ventricular septal defect and the fetus with duplication had cerebral ventricle dilation. Conclusion Our study highlights the phenotypic variability associated with 17p11.2 variations in China. The results further expand the phenotypic spectrum of SMS/PTLS and increase awareness of these disruptive mutations among clinicians.

Copy number variations in multicystic dysplastic kidney: update for prenatal diagnosis and genetic counseling

2016 ◽  
Vol 36 (5) ◽  
pp. 463-468 ◽  
Author(s):  
Qi Xi ◽  
Xiangyu Zhu ◽  
Yaping Wang ◽  
Tong Ru ◽  
Chenyan Dai ◽  
...  
Keyword(s):  
Genetic Counseling ◽  
Prenatal Diagnosis ◽  
Copy Number ◽  
Copy Number Variations ◽  
Multicystic Dysplastic Kidney ◽  
Dysplastic Kidney

X-linked CNV and skewed X-chromosome inactivation

2020 ◽  
pp. 19-21
Author(s):  
Е.А. Фонова ◽  
Е.Н. Толмачева ◽  
А.А. Кашеварова ◽  
М.Е. Лопаткина ◽  
К.А. Павлова ◽  
...  
Keyword(s):  
Cell Proliferation ◽  
Intellectual Disability ◽  
X Chromosome ◽  
Copy Number ◽  
Copy Number Variations ◽  
X Chromosome Inactivation ◽  
Chromosome Inactivation ◽  
Chromosome X ◽  
Skewed X Chromosome Inactivation

Смещение инактивации Х-хромосомы может быть следствием и маркером нарушения клеточной пролиферации при вариациях числа копий ДНК на Х-хромосоме. Х-сцепленные CNV выявляются как у женщин с невынашиванием беременности и смещением инактивации Х-хромосомы (с частотой 33,3%), так и у пациентов с умственной отсталостью и смещением инактивацией у их матерей (с частотой 40%). A skewed X-chromosome inactivation can be a consequence and a marker of impaired cell proliferation in the presence of copy number variations (CNV) on the X chromosome. X-linked CNVs are detected in women with miscarriages and a skewed X-chromosome inactivation (with a frequency of 33.3%), as well as in patients with intellectual disability and skewed X-chromosome inactivation in their mothers (with a frequency of 40%).

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