An algorithm for interpreting the clinical significance of chromosomal microduplications in undifferentiated forms of intellectual disorders

Integral Component ◽

Number Variation ◽

Chromosomal Diseases ◽

Practical Task

Идентификация хромосомных аномалий на субмикроскопическом уровне и установление их роли в этиологии интеллектуальных расстройств являются важной научной и практической задачей. Оценка патогенного значения менее изученного типа вариаций копийности ДНК - хромосомных микродупликаций представляет актуальный предмет для обсуждения. В исследовании предложен алгоритм интерпретации клинической значимости частичных трисомий, который является неотъемлемой составляющей в диагностике и профилактике хромосомных болезней. The identification of chromosomal abnormalities at the submicroscopic level and the establishment of their role in the etiology of intellectual disorders are an important scientific and practical task. Evaluation of the pathogenic value of the less studied type of copy number variation - chromosomal microduplication - is an actual issue. The study proposed an algorithm for interpreting the clinical significance of partial trisomies, which is an integral component in the diagnosis and prevention of chromosomal diseases.

Application of Copy Number Variation Sequencing in Genetic Analysis of Miscarriages in Early and Middle Pregnancy

Cytogenetic and Genome Research ◽

10.1159/000512801 ◽

2020 ◽

Vol 160 (11-12) ◽

pp. 634-642

Author(s):

Shiqiang Luo ◽

Xingyuan Chen ◽

Tizhen Yan ◽

Jiaolian Ya ◽

Zehui Xu ◽

...

Keyword(s):

Copy Number Variation ◽

High Throughput ◽

Copy Number ◽

High Throughput Sequencing ◽

Pregnancy Termination ◽

Mendelian Inheritance ◽

Copy Number Variations ◽

Abnormal Chromosome ◽

High-throughput sequencing based on copy number variation (CNV-seq) is commonly used to detect chromosomal abnormalities. This study identifies chromosomal abnormalities in aborted embryos/fetuses in early and middle pregnancy and explores the application value of CNV-seq in determining the causes of pregnancy termination. High-throughput sequencing was used to detect chromosome copy number variations (CNVs) in 116 aborted embryos in early and middle pregnancy. The detection data were compared with the Database of Genomic Variants (DGV), the Database of Chromosomal Imbalance and Phenotype in Humans using Ensemble Resources (DECIPHER), and the Online Mendelian Inheritance in Man (OMIM) database to determine the CNV type and the clinical significance. High-throughput sequencing results were successfully obtained in 109 out of 116 specimens, with a detection success rate of 93.97%. In brief, there were 64 cases with abnormal chromosome numbers and 23 cases with CNVs, in which 10 were pathogenic mutations and 13 were variants of uncertain significance. An abnormal chromosome number is the most important reason for embryo termination in early and middle pregnancy, followed by pathogenic chromosome CNVs. CNV-seq can quickly and accurately detect chromosome abnormalities and identify microdeletion and microduplication CNVs that cannot be detected by conventional chromosome analysis, which is convenient and efficient for genetic etiology diagnosis in miscarriage.

Implications of copy number variation in people with chromosomal abnormalities: potential for greater variation in copy number state may contribute to variability of phenotype

The HUGO Journal ◽

10.1007/s11568-010-9144-z ◽

2010 ◽

Vol 4 (1-4) ◽

pp. 1-9 ◽

Cited By ~ 5

Author(s):

Adam J. de Smith ◽

Anne L. Trewick ◽

Alexandra I. F. Blakemore

Keyword(s):

Copy Number Variation ◽

Copy Number ◽

Copy Number State ◽

Number State ◽

Clinical diagnosis of single-gene disorders and chromosomal abnormalities based on BGISEQ-500 platform

10.1101/675991 ◽

2019 ◽

Author(s):

Yanqiu Liu ◽

Liangwei Mao ◽

Xiaoming Wei ◽

Jianfen Man ◽

Wenqian Zhang ◽

...

Keyword(s):

Copy Number Variation ◽

Clinical Diagnosis ◽

High Throughput ◽

Copy Number ◽

Genomic Copy Number ◽

Genomic Copy ◽

Monogenic Diseases ◽

Number Variation ◽

Genomic Copy Number Variation

AbstractMost of the variation in the human genome is a single nucleotide variation (SNV) based on a single base or small fragment insertions and deletions and genomic copy number variation (CNV). Both types of mutations are involved in many human diseases. Such diseases often have complex clinical symptoms and difficult clinical diagnosis, so an effective detection method is needed to help clinical diagnosis and prevent birth defects. With the development of sequencing technology, the method of chip capture combined with high-throughput sequencing has been extensively used because of its high throughput, high accuracy, high speed and low cost. This study designed a chip that captures the coding region of 3043 genes associated with 4013 monogenic diseases. In addition, 148 chromosomal abnormalities can be identified by setting targets in specific regions. Compared with the whole exon chip, the chip can detect 4013 monogenic diseases and 148 chromosomal abnormalities at a lower cost, including SNV, intra-gene CNV and genomic copy number variation. This study utilized a strategy of combining the BGISEQ500 sequencing platform with the chip to identify 102 disease-associated mutations in 63 patients, 69 of which were new mutations. The evaluation test results also show that this combination complies with the requirements of clinical testing and has good clinical application value.

Clinical Significance of De Novo and Inherited Copy-Number Variation

Human Mutation ◽

10.1002/humu.22442 ◽

2013 ◽

Vol 34 (12) ◽

pp. 1679-1687 ◽

Cited By ~ 71

Author(s):

Anneke T. Vulto-van Silfhout ◽

Jayne Y. Hehir-Kwa ◽

Bregje W.M. van Bon ◽

Janneke H.M. Schuurs-Hoeijmakers ◽

Stephen Meader ◽

...

Keyword(s):

Copy Number Variation ◽

Clinical Significance ◽

Copy Number ◽

De Novo ◽

Clinical significance of germline copy number variation in susceptibility of human diseases

Journal of Genetics and Genomics ◽

10.1016/j.jgg.2018.01.001 ◽

2018 ◽

Vol 45 (1) ◽

pp. 3-12 ◽

Cited By ~ 7

Author(s):

Liwen Hu ◽

Xinyue Yao ◽

Hairong Huang ◽

Zhong Guo ◽

Xi Cheng ◽

...

Keyword(s):

Copy Number Variation ◽

Clinical Significance ◽

Copy Number ◽

Human Diseases ◽

Efficacy of copy-number variation sequencing technology in prenatal diagnosis

Journal of Perinatal Medicine ◽

10.1515/jpm-2019-0005 ◽

2019 ◽

Vol 47 (6) ◽

pp. 651-655 ◽

Cited By ~ 2

Author(s):

Xiaoxi Zhao ◽

Lin Fu

Keyword(s):

Prenatal Diagnosis ◽

Copy Number Variation ◽

Copy Number ◽

Sex Chromosome ◽

Karyotype Analysis ◽

Balanced Translocation ◽

Combined Application ◽

Number Variation ◽

Medical University

Abstract Background Classical karyotyping and copy-number variation sequencing (CNV-seq) are useful methods for the prenatal detection of chromosomal abnormalities. Here, we examined the potential of using a combination of the two methods for improved and accurate diagnosis. Methods From February 2013 to January 2018, 64 pregnant women showing indications for fetal chromosomal examination in the affiliated hospital of the Inner Mongolia Medical University were selected for this study. Amniotic fluid was collected and used for karyotype analysis and CNV-seq. Results Karyotype analysis of the 64 cases showed that six cases (9.38%) had chromosomal abnormalities. Using CNV-seq, in addition to three cases with numerical abnormalities of chromosomes, 14 cases were detected with CNV, of which five were pathogenic CNV, four were of uncertain clinical significance and five were polymorphic CNV. However, CNV-seq failed to detect one case with sex chromosome mosaicism and a balanced translocation carrier. The rate of abnormal chromosome and CNV detection was 26.56% (17/64) by CNV-seq. Conclusion Application of CNV-seq in prenatal diagnosis could allow the detection of submicroscopic chromosomal abnormalities and effectively reduce the birth of children with microdeletion and microduplication syndrome. Additionally, the combined application of karyotype analysis and CNV-seq can effectively improve the detection rate of chromosome abnormalities.