Performance of Chromosomal Microarray Analysis for Detection of Copy Number Variations in Fetal Echogenic Bowel

Williams-Beuren Syndrome (WBS; OMIM #194050) is a rare neurodevelopmental disorder that results from a deletion at 7q11.23 spanning 25-27 genes. We performed chromosomal microarray analysis (CMA) in 9 Taiwanese patients with WBS to confirm the diagnosis. These samples had already been examined by FISH and diagnosed as WBS. Pathogenic copy number variations (CNVs) were identified in all patients, including 24 genes (spanning from FKBP6 to GTF2I) with typical 7q11.23 microdeletion. A deletion in TRIM50 was common in Taiwanese patients with WBS (8/9). Furthermore, 1 patient had 2 additional gene deletions in NCF1 and GTF2IRD2. We also found 4 patients with duplications of 4p16.1, 16p13.11, 10q26.3, and 21q22.3. All 9 WBS patients exhibited distinctive facial dysmorphisms, including a wide mouth, thick prominent lips, short nose with anteverted nares, and periorbital puffiness. However, cardiac defects were not frequent in our patients (3/9). In conclusion, we detected CNVs associated with WBS in a Taiwanese population using CMA. Although CMA is expensive and labor-intensive, it is useful for identifying typical/atypical CNVs, delineating distal break points, and detecting other CNVs.

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Chromosomal microarray analysis as the first-tier test for the identification of pathogenic copy number variants in chromosome 9 pericentric regions and its challenge

Molecular Cytogenetics ◽

10.1186/s13039-016-0272-6 ◽

2016 ◽

Vol 9 (1) ◽

Cited By ~ 1

Author(s):

Jia-Chi Wang ◽

Fatih Z. Boyar

Keyword(s):

Microarray Analysis ◽

Copy Number ◽

Copy Number Variants ◽

Chromosome 9 ◽

Chromosomal Microarray ◽

Chromosomal Microarray Analysis

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Clinical utility of chromosomal microarray analysis to detect copy number variants: Experience in a single tertiary hospital

Journal of Genetic Medicine ◽

10.5734/jgm.2021.18.1.31 ◽

2021 ◽

Vol 18 (1) ◽

pp. 31-37

Author(s):

Hee Sue Park ◽

Aryun Kim ◽

Kyeong Seob Shin ◽

Bo Ra Son

Keyword(s):

Microarray Analysis ◽

Copy Number ◽

Clinical Utility ◽

Copy Number Variants ◽

Tertiary Hospital ◽

Chromosomal Microarray ◽

Chromosomal Microarray Analysis

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Comprehensive Evaluation of Non-invasive Prenatal Screening to Detect Fetal Copy Number Variations

Frontiers in Genetics ◽

10.3389/fgene.2021.665589 ◽

2021 ◽

Vol 12 ◽

Author(s):

Jing Wang ◽

Bin Zhang ◽

Lingna Zhou ◽

Qin Zhou ◽

Yingping Chen ◽

...

Keyword(s):

Prenatal Diagnosis ◽

Pregnant Women ◽

Copy Number ◽

Prenatal Screening ◽

Comprehensive Evaluation ◽

Copy Number Variations ◽

Chromosomal Microarray ◽

Chromosomal Microarray Analysis ◽

Non Invasive ◽

Pathogenic Cnvs

ObjectiveTo evaluate the effectiveness of non-invasive prenatal screening (NIPS) in prenatal screening of fetal pathogenic copy number variants (CNVs).Materials and MethodsWe evaluated the prenatal screening capacity using traditional and retrospective approaches. For the traditional method, we evaluated 24,613 pregnant women who underwent NIPS; cases which fetal CNVs were suggested underwent prenatal diagnosis with chromosomal microarray analysis (CMA). For the retrospective method, we retrospectively evaluated 47 cases with fetal pathogenic CNVs by NIPS. A systematic literature search was performed to compare the evaluation efficiency.ResultsAmong the 24,613 pregnant women who received NIPS, 124 (0.50%) were suspected to have fetal CNVs. Of these, 66 women underwent prenatal diagnosis with CMA and 13 had true-positive results. The positive predictive value (PPV) of NIPS for fetal CNVs was 19.7%. Among 1,161 women who did not receive NIPS and underwent prenatal diagnosis by CMA, 47 were confirmed to have fetal pathogenic CNVs. Retesting with NIPS indicated that 24 of these 47 cases could also be detected by NIPS, representing a detection rate (DR) of 51.1%. In total, 10 publications, namely, six retrospective studies and four prospective studies, met our criteria and were selected for a detailed full-text review. The reported DRs were 61.10–97.70% and the PPVs were 36.11–80.56%. The sizes of CNVs were closely related to the accuracy of NIPS detection. The DR was 41.9% (13/31) in fetuses with CNVs ≤ 3 Mb, but was 55.0% (11/20) in fetuses with CNVs > 3 Mb. Finally, to intuitively show the CNVs accurately detected by NIPS, we mapped all CNVs to chromosomes according to their location, size, and characteristics. NIPS detected fetal CNVs in 2q13 and 4q35.ConclusionThe DR and PPV of NIPS for fetal CNVs were approximately 51.1% and 19.7%, respectively. Follow-up molecular prenatal diagnosis is recommended in cases where NIPS suggests fetal CNVs.

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255: First trimester serum analytes as predictors of pathologic copy number variants (CNV) on chromosomal microarray analysis (CMA)

American Journal of Obstetrics and Gynecology ◽

10.1016/j.ajog.2017.10.183 ◽

2018 ◽

Vol 218 (1) ◽

pp. S164

Author(s):

Moti Gulersen ◽

Michael Divon ◽

Stephanie Baum ◽

David Krantz ◽

Kristen Maliszewski ◽

...

Keyword(s):

Microarray Analysis ◽

Copy Number ◽

Copy Number Variants ◽

First Trimester ◽

Chromosomal Microarray ◽

Chromosomal Microarray Analysis

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Phenotypic and Molecular Cytogenetic Analysis of a Case of Monosomy 1p36 Syndrome due to Unbalanced Translocation

Molecular Syndromology ◽

10.1159/000510428 ◽

2020 ◽

Vol 11 (5-6) ◽

pp. 284-295

Author(s):

Dalia F. Hussen ◽

Alaa K. Kamel ◽

Mona K. Mekkawy ◽

Engy A. Ashaat ◽

Mona O. El Ruby

Keyword(s):

Intellectual Disability ◽

Microarray Analysis ◽

Cytogenetic Analysis ◽

Copy Number ◽

Clinical Manifestations ◽

Copy Number Variations ◽

Chromosomal Microarray Analysis ◽

Fish Analysis ◽

Unbalanced Translocation ◽

Genotype Correlation

Monosomy 1p36 syndrome is one of the most common submicroscopic deletion syndromes, which is characterized by the presence of delayed developmental milestones, intellectual disability, and clinically recognizable dysmorphic craniofacial features. The syndrome comprises 4 cytogenetic groups including pure terminal deletions, interstitial deletions, complex rearrangements, and derivative chromosomes 1 due to unbalanced translocations, where unbalanced translocations represent the least percentage of all cases of monosomy 1p36 (7%). Most patients with monosomy 1p36 due to an unbalanced translocation can be cytogenetically diagnosed using conventional techniques. However, chromosomal microarray analysis is mandatory in these cases to detect copy number variance and size of the deletion and allows for setting a phenotype-genotype correlation. Here, we studied a 1.5-year-old female patient who showed intellectual disability, delayed milestones, hypotonia, seizures, and characteristic dysmorphic features including brachycephaly, straight eyebrows, deep-set eyes, downslanting palpebral fissures, midface hypoplasia, depressed nasal bridge, long philtrum, and pointed chin. Conventional cytogenetic analysis (CCA), microarray study, and fluorescence in situ hybridization (FISH) analysis were performed. CCA showed a translocation involving chromosomes 1 and 21, 45,XX,der(1)t(1;21)(p36.32;q21.1)dn. Microarray analysis revealed copy number losses at both 1p36 and proximal 21q. FISH confirmed the presence of the 1p36 deletion, but was not performed for 21q. We have concluded that phenotype-genotype correlation for monosomy 1p36 syndrome can be performed for the fundamental clinical manifestations; however, the final aspect of the syndrome depends on composite factors. Monosomy 1p36 due to unbalanced translocation may present either classically or with additional altered features of various severity based on the copy number variations involving different chromosomes.

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Application of Chromosome Microarray Analysis in the Investigation of Developmental Disabilities and Congenital Anomalies: Single Center Experience and Review of NRXN3 and NEDD4L Deletions

Molecular Syndromology ◽

10.1159/000509645 ◽

2020 ◽

Vol 11 (4) ◽

pp. 197-206

Author(s):

Alper Han Çebi ◽

Şule Altıner

Keyword(s):

Developmental Disabilities ◽

Microarray Analysis ◽

Congenital Anomalies ◽

Copy Number Variations ◽

Step Test ◽

Chromosomal Microarray ◽

Chromosomal Microarray Analysis ◽

Multiple Congenital Anomalies ◽

Single Center Experience ◽

Genome Wide

Chromosomal microarray analysis (CMA) is a first step test used for the diagnosis of patients with developmental delay, intellectual disability, autistic spectrum disorder, and multiple congenital anomalies. Its widespread usage has allowed genome-wide identification of copy number variations (CNVs). In our study, we performed a retrospective study on clinical and microarray data of 237 patients with developmental disabilities and/or multiple congenital anomalies and investigated the clinical utility of CMA. Phenotype-associated CNVs were detected in 15.18% of patients. Besides, we detected submicroscopic losses on 14q24.3q31.1 in a patient with speech delay and on 18q21.31q21.32 in twin patients with seizures. Deletions of <i>NRXN3</i> and <i>NEDD4L</i> were responsible for the phenotypes, respectively. This study showed that CMA is a powerful diagnostic tool in this patient group and expands the genotype-phenotype correlations on developmental disabilities.

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