OP06.03: Prenatal diagnosis of central nervous system anomalies by high-resolution chromosomal microarray analysis

The aims of this study were to evaluate the contribution of chromosomal microarray analysis (CMA) in the prenatal diagnosis of fetuses with central nervous system (CNS) anomalies but normal chromosomal karyotype. A total of 46 fetuses with CNS anomalies with or without other ultrasound anomalies but normal karyotypes were evaluated by array-based comparative genomic hybridisation (aCGH) or single-nucleotide polymorphism (SNP) array. The result showed that CNVs were detected in 17 (37.0%) fetuses. Of these, CNVs identified in 5 (5/46, 10.9%) fetuses were considered to be likely pathogenic, and CNVs detected in 3 (3/46, 6.5%) fetuses were defined as being of uncertain clinical significance. Fetuses with CNS malformations plus other ultrasound anomalies had a higher rate of pathogenic CNVs than those with isolated CNS anomalies (13.6% versus 8.3%), but there was no significant difference (Fisher’s exact test,P>0.05). Pathogenic CNVs were detected most frequently in fetuses with Dandy-Walker syndrome (2/6, 33.3%) when compared with other types of neural malformations, and holoprosencephaly (2/7, 28.6%) ranked the second. CMA is valuable in prenatal genetic diagnosis of fetuses with CNS anomalies. It should be considered as part of prenatal diagnosis in fetuses with CNS malformations and normal karyotypes.

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Detection of submicroscopic chromosomal aberrations by chromosomal microarray analysis for the prenatal diagnosis of central nervous system abnormalities

Journal of Clinical Laboratory Analysis ◽

10.1002/jcla.23434 ◽

2020 ◽

Vol 34 (10) ◽

Author(s):

Tingting Song ◽

Ying Xu ◽

Yu Li ◽

Li Jia ◽

Jiao Zheng ◽

...

Keyword(s):

Central Nervous System ◽

Nervous System ◽

Prenatal Diagnosis ◽

Microarray Analysis ◽

Chromosomal Aberrations ◽

Chromosomal Microarray ◽

Chromosomal Microarray Analysis

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The use of chromosomal microarray analysis for diagnostics of chromosomal pathology in fetal central nervous system malformations

Obstetrics Gynecology and Reproduction ◽

10.17749/2313-7347/ob.gyn.rep.2020.160 ◽

2020 ◽

Vol 14 (4) ◽

pp. 449-456

Author(s):

J. K. Kievskaya ◽

I. V. Kanivets ◽

E. V. Kudryavtseva ◽

D. V. Pyankov ◽

S. A. Korostelev

Keyword(s):

Central Nervous System ◽

Nervous System ◽

Microarray Analysis ◽

Congenital Malformations ◽

Copy Number Variations ◽

Chromosomal Microarray ◽

Chromosomal Microarray Analysis ◽

Chromosome Microarray Analysis ◽

Pathogenic Cnvs ◽

Chromosome Microarray

Introduction. The prevalence of congenital malformations (CMFs) in fetal central nervous system (CNS) ranges from 1.5 to 3 % and covers around 29 % among all malformations, whereas percentage in the structure of perinatal and infant mortality reaches 25–26 %.Aim: to estimate frequency of pathogenic copy number variations (CNVs) in fetuses with congenital malformations of CNS and normal karyotyping cytogenetic analysis.Materials and Methods. There were enrolled 42 pregnant women underwent invasive prenatal diagnostics in 2013–2019 due to ultrasound detection of congenital CNS defect in fetus. Fetal samples were studied by using chromosome microarray analysis (CMA).Results. Various pathogenic CNVs were detected in 7 (16.6 %) fetuses with prenatally diagnosed congenital CNS malformations. Non-syndrome pathogenic CNVs were detected in 85.7 %.Conclusion. Thus, performing chromosome microarray analysis as the first-line assay allows to diagnose not only aneuploidy, but also microdeletion/microduplication, the size of which below resolution threshold for standard cytogenetic karyotyping

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Clinical utility of comprehensive genomic profiling in central nervous system tumors of children and young adults

Neuro-Oncology Advances ◽

10.1093/noajnl/vdab037 ◽

2021 ◽

Vol 3 (1) ◽

Author(s):

Jianling Ji ◽

Kristiyana Kaneva ◽

Matthew C Hiemenz ◽

Girish Dhall ◽

Tom Belle Davidson ◽

...

Keyword(s):

Central Nervous System ◽

Nervous System ◽

Clinical Utility ◽

Adolescent And Young Adult ◽

Cns Tumors ◽

Chromosomal Microarray ◽

Chromosomal Microarray Analysis ◽

Genomic Profiling ◽

Comprehensive Genomic Profiling ◽

Clinically Significant

Abstract Background Recent large-scale genomic studies have revealed a spectrum of genetic variants associated with specific subtypes of central nervous system (CNS) tumors. The aim of this study was to determine the clinical utility of comprehensive genomic profiling of pediatric, adolescent and young adult (AYA) CNS tumors in a prospective setting, including detection of DNA sequence variants, gene fusions, copy number alterations (CNAs), and loss of heterozygosity. Methods OncoKids, a comprehensive DNA- and RNA-based next-generation sequencing (NGS) panel, in conjunction with chromosomal microarray analysis (CMA) was employed to detect diagnostic, prognostic, and therapeutic markers. NGS was performed on 222 specimens from 212 patients. Clinical CMA data were analyzed in parallel for 66% (146/222) of cases. Results NGS demonstrated clinically significant alterations in 66% (147/222) of cases. Diagnostic markers were identified in 62% (138/222) of cases. Prognostic information and targetable genomic alterations were identified in 22% (49/222) and 18% (41/222) of cases, respectively. Diagnostic or prognostic CNAs were revealed by CMA in 69% (101/146) of cases. Importantly, clinically significant CNAs were detected in 57% (34/60) of cases with noncontributory NGS results. Germline cancer predisposition testing was indicated for 27% (57/212) of patients. Follow-up germline testing was performed for 20 patients which confirmed a germline pathogenic/likely pathogenic variant in 9 cases: TP53 (2), NF1 (2), SMARCB1 (1), NF2 (1), MSH6 (1), PMS2 (1), and a patient with 47,XXY Klinefelter syndrome. Conclusions Our results demonstrate the significant clinical utility of integrating genomic profiling into routine clinical testing for pediatric and AYA patients with CNS tumors.

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Chromosomal Microarray Analysis and Prenatal Diagnosis

Obstetrical & Gynecological Survey ◽

10.1097/ogx.0000000000000119 ◽

2014 ◽

Vol 69 (10) ◽

pp. 613-621 ◽

Cited By ~ 8

Author(s):

Jamie O. Lo ◽

Brian L. Shaffer ◽

Cori D. Feist ◽

Aaron B. Caughey

Keyword(s):

Prenatal Diagnosis ◽

Microarray Analysis ◽

Chromosomal Microarray ◽

Chromosomal Microarray Analysis

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15q23 Gain in a Neonate with a Giant Omphalocele and Multiple Co-Occurring Anomalies

Case Reports in Pediatrics ◽

10.1155/2018/8702568 ◽

2018 ◽

Vol 2018 ◽

pp. 1-5

Author(s):

Hui-Fang Zhou ◽

Christopher J. O’Conor ◽

Chiraag Gangahar ◽

Louis P. Dehner

Keyword(s):

High Resolution ◽

Abdominal Wall ◽

Microarray Analysis ◽

Abdominal Wall Defect ◽

Conventional Technique ◽

Chromosomal Microarray ◽

Chromosomal Microarray Analysis ◽

Genetic Abnormality ◽

Initial Report ◽

Giant Omphalocele

Background. Omphalocele is a rare congenital abdominal wall defect. It is frequently associated with genetic abnormality and other congenital anomalies, although isolated omphalocele cases do exist. Data have shown that omphalocele with co-occurring genetic abnormality has worse prognosis than isolated omphalocele. Chromosomal analysis by a conventional technique such as karyotyping can only detect aneuploidy and large segmental duplication or deletion. Newer techniques such as high-resolution microarray analysis allow for the study of alterations in chromosomal segments that are less than 5 Mb in length; this has led to identification of critical region and genes in the pathogenesis of omphalocele. Case Presentation. The current study is the initial report of a newborn male with a 15q23 gain and a giant omphalocele. High-resolution chromosomal microarray analysis identified this gain of copy number spanned 676 kb, involving almost the entire NOX5 gene (except for exon 1 of the longer transcript), the entirety of the EWSAT1, GLCE, PAQR5, KIF23, RPLP1, and DRAIC genes and exons 1–3 of the PCAT29 gene. Conclusion. To date, this is the first report of an associated 15q23 gain in a case with omphalocele. Interestingly, Giancarlo Ghiselli and Steven A Farber have reported that GLCE knockdown impairs abdominal wall closure in zebrafish. We also identified GLCE gene alteration in our case. This highlights the importance of GLCE in abdominal wall development. Further study of the function of GLCE and other genes might lead to a better understanding of the molecular mechanism of omphalocele.

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