Genetic analysis of a family with 6q22 microdeletion and 10p15.3p13 microduplication in two consecutive pregnancies / 中华检验医学杂志

Objective:Cytogenetic and molecular genetic analysis was performed on two consecutive antenatal abnormal fetuses and their parents in a family to clarify the copy number variation(CNV) and its mechanism.Methods:The karyotypes of two fetuses and their parents were analyzed by conventional karyotyping techniques, and CNVs of two fetuses and their mother were analyzed by low-coverage whole-genome copy number variation sequencing (CNV-seq) techniques.Results:The amniotic fluid karyotype results of fetus 1 and 2 were 46, XN, der(4)t(4;10)(q35;p13). The mother′s peripheral blood karyotype result was 46, XX, t(4;10)(q35;p13), and the father′s karyotype was normal. The CNV-seq results of fetus 1 and 2 were seq[hg19]6q22.31(122740000-125440000)X1; 10p15.3p13(120000-17260000)X3, suggesting that there was a heterozygous deletion of about 2 700 000 bp in fetal 6q22.31 and a duplication of about 17 140 000 bp in fetal 10p15.3p13. The CNV-seq result of their mother was seq[hg19]6q22.31(122740000-125440000)X1, suggesting that there was a heterozygous deletion of about 2 700 000 bp in 6q22.31. The pregnant woman and her family chose to terminate the pregnancy after genetic consulting.Conclusion:The combined application of karyotyping and CNV-Seq is significantly beneficial to detecting microdeletions or microduplications of fetal chromosomes and effectively preventing the birth of defective children.

Application of genome copy number variation sequencing combined with chromosome karyotype analysis in prenatal diagnosis / 中国医师进修杂志

Objective:To explore the application value of copy number variation sequencing(CNV-seq) combined with chromosome karyotyping technology based on next-generation sequencing technology in prenatal diagnosis.Methods:The subjects of the study were 329 pregnant women who underwent prenatal diagnosis at Dalian Municipal Women and Children′s Medical Center from January 2019 to June 2020. The amniotic fluid samples of these pregnant women were submitted for chromosome karyotype analysis, and CNV-seq testing was performed at the same time to compare the test results of the two methods.Results:A total of 53 cases of abnormal chromosomes were detected using CNV-seq combined with chromosome karyotyping technology, with an abnormal detection rate of 16.11%(53/329). Among them, 26 cases had consistent detection results, including 22 cases of aneuploidy, 2 cases of structural abnormalities and 2 cases of mosaic; CNV-seq detected 23 cases of chromosome copy number variations that were missed by karyotyping, including 17 cases of microdeletion and 6 cases of microduplication; chromosome karyotype analysis detected 4 cases of chromosome structural abnormalities that were missed by CNV-seq, including 3 cases balanced translocation and 1 case of inversion.Conclusions:CNV-seq has obvious advantages in detecting copy number variations of small fragments, which can make up for the lack of resolution of karyotyping analysis; CNV-seq combined with chromosome karyotyping analysis can improve the detection rate of abnormal chromosomes, which is important for prenatal diagnosis meaning.

Diagnosis of one case of Williams-Beuren syndrome presenting with hypothyroidism by low-coverage massively parallel CNV sequencing / 中华内分泌代谢杂志

Objective@#To explore the clinical phenotypes and the genetic causes for a 5 years old boy with unexplained growth retardation, developmental delay, special face, and hypothyroidism.@*Methods@#Routine G-banding was performed to analyze the karyotype of the patient and his parents. In addition, whole exome sequencing and low-coverage massively parallel CNV sequencing (CNV-seq) were used to determine the potentially pathogenic variants as well as the copy number variations (CNVs).@*Results@#The child′s karyotype was 46, XY, and his parents′ karyotypes were normal.However, CNV-seq identified a heterozygous deletion of 1.56 Mb on chromosome region 7q11.23 in the patient, including 24 protein-coding genes, which were associated with Williams-Beuren syndrome. His parents′ results of CNV-seq were normal, indicating a de novo CNVs.@*Conclusion@#A Williams-Beuren syndrome child presenting with hypothyroidism was diagnosed by CNV-seq, which would contribute to further understanding the clinical phenotypes and pathogenesis of this disease.

Comparative study of copy number variation sequencing and karyotype analysis in detection of chromosome abnormality / 西安交通大学学报(医学版)

Objective: To explore the clinical application of copy number variation sequencing (CNV-seq) and karyotype analysis in detection of chromosome abnormality. Methods: Chromosome of 42 patients was analyzed by karyotype analysis and CNV-seq. The advantages and limitations of the two methods were observed and compared. Results: We detected 7 cases of copy number variation by CNV-seq and the case detection rate was 16.67%. We detected cases of chromosomal anomalies by karyotype analysis, which included 6 cases of structural chromosome aberration and 2 cases of chromosome numerical abnormality. The case detection rate of karyotype analysis was 19.04%. Moreover, 4 cases of chromosome polymorphism were analyzed. Conclusion: CNV-seq can be applied in examining the abnormal chromosome number and structural aberrations, especially in providing clinically significant cytogenetic information that is difficult to be determined by karyotype analysis. It can also analyze chromosome microdeletion and microduplication syndrome with a chromosome resolution of 0.1 Mb. However, CNV-seq fails to identify balanced chromosomal translocation and inversion. Therefore, a combination of karyotype analysis and CNV-seq will provide accurate clinical diagnosis for patients with chromosome abnormality.