PMC6506918_01
PMC6506918_02
PMC6506918_03
(A) Location of the deletion within banding region 9q21.33q22.31 and (B) close view
shows a 7.0-Mb deletion overlaid on the raw log2 probe plot. Chromosomal microarray
analysis was performed using array comparative genomic hybridization (aCGH) with
Agilent's SurePrint G3 4x180 k CGH+ single-nucleotide polymorphism (SNP). Array CGH
data were analyzed using Cytogenomics (v.3.0.2.11, Agilent) and Bench LAB CNV (v5.1.1,
Cartagenia).
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PMC6506918_03_10.1177_2329048X19844920-fig1.jpg
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Technologies, Santa Clara, CA) led to the identification of a heterozygous 7.0-Mb deletion of chromosome 9q21.33q22.31 (chr9:87,331,806-94,336,693) (Figure 1).
The size, extent, and genomic content of the deletion in this patient. Genomic
coordinates from array comparative genomic hybridization (aCGH,
chr9:87,331,806-94,336,693 [hg19]) were analyzed on UCSC genome browser. UCSC genome
browser tracks (hg19) showing (A) all genes (RefSeq) (B) OMIM genes (green bars) (C)
Database of Genomic Variants (DGV).
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The deletion included 45 genes and transcripts and had only minimal overlap with copy number variants (CNVs) reported among healthy individuals in the Database of Genomic Variants (DGV; http://dgv.tcag.ca) (Figure 2). The interstitial 9q21.33q22.31 deletion was confirmed by fluorescence in situ hybridization (FISH) in all interphase nuclei using a bacterial artificial chromosome (BAC) probe that hybridized to the 9q21.33 region and a control probe specific to the subtelomeric region of chromosome 9q (Figure 3).
The identified deletion was confirmed by fluorescence in situ hybridization (FISH)
using a bacterial artificial chromosome (BAC) probe targeted to the 9q21.33 region
(RP11- 91M3, Empire Genomics) and a control probe specific to the subtelomeric region
of chromosome 9q (TelVysion 9q, D9S325, Abbott Molecular). Loss of the green
fluorescent hybridization signal confirmed the deletion in the nuclei. Chromosomes
were stained with DAPI.
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PMC6506918_03_10.1177_2329048X19844920-fig3.jpg
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The deletion included 45 genes and transcripts and had only minimal overlap with copy number variants (CNVs) reported among healthy individuals in the Database of Genomic Variants (DGV; http://dgv.tcag.ca) (Figure 2). The interstitial 9q21.33q22.31 deletion was confirmed by fluorescence in situ hybridization (FISH) in all interphase nuclei using a bacterial artificial chromosome (BAC) probe that hybridized to the 9q21.33 region and a control probe specific to the subtelomeric region of chromosome 9q (Figure 3).
Parental analysis by array comparative genomic hybridization (aCGH) showed that
neither parent was a carrier of this aberration, indicating that the deletion occurred
de novo in the proband.
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fig4-2329048X19844920
Subsequent parental CMA testing determined that the 7.0-Mb interstitial deletion was not inherited and, therefore, occurred de novo in this patient (Figure 4).