Molecular cytogenetic identification of small supernumerary marker chromosomes using chromosome microarray analysis

Xue, Huili; Huang, Hailong; Wang, Yan; An, Gang; Zhang, Min; Xu, Liangpu; Lin, Yuan

doi:10.1186/s13039-019-0425-5

Cited by 10 publications

(9 citation statements)

References 27 publications

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“…Whole genomic DNA was extracted from amniocytes or fetal cord blood of each fetus and its parents using the QIAamp DNA Blood Mini Kit (Qiagen, Valencia, CA). The DNA was examined by SNP array analysis using the CytoScan 750 K Array (Affymetrix, Santa Clara, CA) containing 200,000 SNPs and 550,000 CNVs as previously described 13 . The results were analyzed using the Chromosome Analysis Suite software (Affymetrix) and annotated based on GRCh37 (hg19).…”

Section: Methodsmentioning

confidence: 99%

Detection of copy number variation associated with ventriculomegaly in fetuses using single nucleotide polymorphism arrays

Xue

Lin

et al. 2021

Sci Rep

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Etiopathogenesis of fetal ventriculomegaly is poorly understood. Associations between fetal isolated ventriculomegaly and copy number variations (CNVs) have been previously described. We investigated the correlations between fetal ventriculomegaly—with or without other ultrasound anomalies—and chromosome abnormalities. 222 fetuses were divided into four groups: (I) 103 (46.4%) cases with isolated ventriculomegaly, (II) 41 (18.5%) cases accompanied by soft markers, (III) 33 (14.9%) cases complicated with central nervous system (CNS) anomalies, and (IV) 45 (20.3%) cases with accompanying anomalies. Karyotyping and single nucleotide polymorphism (SNP) array were used in parallel. Karyotype abnormalities were identified in 15/222 (6.8%) cases. Karyotype abnormalities in group I, II, III, and IV were 4/103 (3.9%), 2/41 (4.9%), 4/33 (12.1%), and 5/45 (11.1%), respectively. Concerning the SNP array analysis results, 31/222 (14.0%) were CNVs, CNVs in groups I, II, III, and IV were 11/103 (10.7%), 6/41 (14.6%), 9/33 (27.3%), and 5/45 fetuses (11.1%), respectively. Detections of clinical significant CNVs were higher in non-isolated ventriculomegaly than in isolated ventriculomegaly (16.81% vs 10.7%, P = 0.19). SNP arrays can effectively identify CNVs in fetuses with ventriculomegaly and increase the abnormal chromosomal detection rate by approximately 7.2%, especially ventriculomegaly accompanied by CNS anomalies.

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Section: Methodsmentioning

confidence: 99%

Detection of copy number variation associated with ventriculomegaly in fetuses using single nucleotide polymorphism arrays

Xue

Lin

et al. 2021

Sci Rep

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“…G-banding analysis (C/NOR-banding when required) at a resolution of approximately 320~400 bands was performed on the parents’ peripheral fetal blood according to standard laboratory protocols and ISCN 2016 [14]. Around 2 ml of parental peripheral blood in the parents of the fetuses was collected in heparin tubes.…”

Section: Methodsmentioning

confidence: 99%

A prenatal diagnosis and genetics study of five pedigrees in the Chinese population with Xp22.31 microduplication

et al. 2019

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BackgroundCopy number variations (CNVs) can contribute to human phenotype, phenotypic diversity and disease susceptibility, while others may benign. In the current study, an attempt to investigate the pathogenicity of CNVs in chromosome Xp22.31 was explored.MethodsG-banding and SNP-array techniques were used to analyze chromosome karyotypes and CNVs in fetuses. Parents associate with five different pedigrees possessing high risk factors in pregnancy were considered with such parameters as advanced age, high risk of serological screening and ultrasound abnormalities.ResultsThe fetuses’ amniotic fluid karyotypes were 46, XX and those of their parents with the five pedigrees revealed no abnormalities. Here, we noticed a series of individuals with Xp22.31 duplications ranging from 534.6 kb to 1.6 Mb. It was detected through SNP array that the fetuses in Pedigree 1 and 2 had ~ 600 kb duplications in the Xp22.31 region of their X chromosomes which contained two OMIM genes, HDHD1 (OMIM: 306480) and part of STS (OMIM: 300747). The fetuses of Pedigrees 3, 4 and 5 had 1.6 Mb duplication in the same chromosome which contained four OMIM genes: HDHD1 (OMIM: 306480), STS (OMIM: 300747), PNPLA4 (OMIM: 300102) and VCX (OMIM: 300229). The duplications in the fetuses of Pedigrees 1 and 5 were inherited from the non-phenotypic parents. Pedigrees 3 and 4 refused to perform parental verification. Finally, four of the five pedigrees continue towards pregnancy with no abnormalities being observed during followed-ups.ConclusionOur study first showed duplications of Xp22.31 in Chinese population. Clinical and genetic investigation on five different pedigrees, we consider the duplication of these fragments as likely benign copy number variants (CNVs). We suggest that the duplications of Xp22.31 with recurrent duplication as a benign CNVs .

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“…Recently published studies indicated that the novel microarray methods such as CMA combined with molecular cytogenetic analysis is particularly effective in the rapid and accurate diagnosis of sSMCs or copy number variations. These combined protocols are especially useful in identifying rare structural chromosomal aberrations prenatally and in assessing the prognosis of fetuses carrying such abnormalities [29]. It is worth of noting that although aCGH identifies the whole gene component of sSMCs and the other underlying chromosomal anomalies too (except for balanced translocations) in one test, it may miss to diagnose sSMCs formed of heterochromatin and the cases with low level of mosaicism [30].…”

Section: Discussionmentioning

confidence: 99%

Prenatal diagnosis of a 16p11.2p11.1 mosaic small supernumerary marker chromosome (sSMC)

Tidrenczel

Tardy

Pikó

et al. 2019

Preprint

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Background. Small supernumerary marker chromosome (sSMC) is a challenge in prenatal diagnosis. Its’ presence is associated with advanced maternal age and distinct ultrasound findings, prediction of postnatal clinical consequences and prenatal counselling is difficult. Exact characterization of an sSMC is augmented by the application of novel molecular methods such as fluorescent in situ hybridization (FISH) and array comparative genome hybridization (aCGH). Case presentation. Chorion villous sampling of a fetus of a 42-year old secundipara was carried out due to advanced maternal age and the conventional banding cytogenetic examination revealed a mosaic sSMC. Detailed prenatal ultrasound scan showed no fetal malformations. The karyotype from confirmatory amniocentesis was 47,XY,+mar[45]/46,XY. The level of mosaicism was 70% from chorionic villus and amnion cells as well. By using FISH and SNP based aCGH the exact origin of the marker was described and the final prenatal karyotype was determined as 47,XY,+mar[70].arr[GRCh38]16p11.2p11.1(31699804_35989873)x3dn/46,XY[30]. The increase in DNA dosage was 4,29 Mb affecting 20 genes with two OMIM ones (ZNF267 and TP53TG3), the SNP analysis excluded the possibility of uniparental disomy (UPD) of the chromosome. The application of the molecular cytogenetic methods allowed us the differentiate the mosaic marker chromosome from the known 16p11.2 duplication syndrome in close neighboring that is connected to developmental delay and autism spectrum disorder. The present case was identified as a harmless de novo euchromatic variant (EV) of the short arm of chromosome 16. Postnatal karyotyping from neonatal peripheral blood confirmed the presence of the marker. FISH analysis with probe D16Z2 on cultured lymphocyte and buccal smear samples revealed a 64% and 45% mosaic state of the sSMC, respectively. The precise karyotype was finally defined as 47,XY,+min(16)(:16p11.2->p11.1:)dn[64]/46,XY. Conclusions. Novel microarray methods combined with molecular cytogenetic analysis is particularly effective in the rapid and accurate diagnosis of sSMCs, especially in a prenatal situation when the exact characterization of a genomic imbalance is of utmost importance. Precise diagnosis facilitates proper genetic counseling, allows informed decision making and helps avoiding unnecessary pregnancy termination.

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Molecular cytogenetic identification of small supernumerary marker chromosomes using chromosome microarray analysis

Cited by 10 publications

References 27 publications

Detection of copy number variation associated with ventriculomegaly in fetuses using single nucleotide polymorphism arrays

Detection of copy number variation associated with ventriculomegaly in fetuses using single nucleotide polymorphism arrays

A prenatal diagnosis and genetics study of five pedigrees in the Chinese population with Xp22.31 microduplication

Prenatal diagnosis of a 16p11.2p11.1 mosaic small supernumerary marker chromosome (sSMC)

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