Korean J Lab Med.  2010 Feb;30(1):70-75. 10.3343/kjlm.2010.30.1.70.

Identification of a Novel Deletion Region in 3q29 Microdeletion Syndrome by Oligonucleotide Array Comparative Genomic Hybridization

• Seo EJ
• Jun KR
• Yoo HW
• Yoo HK
• Lee JO

• KMID: 1096822
• DOI: http://doi.org/10.3343/kjlm.2010.30.1.70

Abstract

BACKGROUND
The 3q29 microdeletion syndrome is a genomic disorder characterized by mental retardation, developmental delay, microcephaly, and slight facial dysmorphism. In most cases, the microdeletion spans a 1.6-Mb region between low-copy repeats (LCRs). We identified a novel 4.0- Mb deletion using oligonucleotide array comparative genomic hybridization (array CGH) in monozygotic twin sisters.
METHODS
G-banded chromosome analysis was performed in the twins and their parents. Highresolution oligonucleotide array CGH was performed using the human whole genome 244K CGH microarray (Agilent Technologies, USA) followed by validation using FISH, and the obtained results were analyzed using the genome database resources.
RESULTS
G-banding revealed that the twins had de novo 46,XX,del(3)(q29) karyotype. Array CGH showed a 4.0-Mb interstitial deletion on 3q29, which contained 39 genes and no breakpoints flanked by LCRs. In addition to the typical characteristics of the 3q29 microdeletion syndrome, the twins had attention deficit-hyperactivity disorder, strabismus, congenital heart defect, and gray hair. Besides the p21-activated protein kinase (PAK2) and discs large homolog 1 (DLG1) genes, which are known to play a critical role in mental retardation, the hairy and enhancer of split 1 (HES1) and antigen p97 (melanoma associated; MFI2) genes might be possible candidate genes associated with strabismus, congenital heart defect, and gray hair.
CONCLUSIONS
The novel 4.0-Mb 3q29 microdeletion found in the twins suggested the occurrence of genomic rearrangement mediated by mechanisms other than nonallelic homologous recombination. Molecular genetic and functional studies are required to elucidate the contribution of each gene to a specific phenotype.

Keyword

Chromosome disorders; Chromosome deletion; Human chromosome pair 3; Microarray analysis; Comparative genomic hybridization

MeSH Terms

Adaptor Proteins, Signal Transducing/genetics
Adolescent
Attention Deficit Disorder with Hyperactivity/genetics
Basic Helix-Loop-Helix Transcription Factors/genetics
*Chromosome Deletion
Chromosome Disorders/*genetics
*Chromosomes, Human, Pair 3
Comparative Genomic Hybridization/*methods
Diseases in Twins/*genetics
Female
Homeodomain Proteins/genetics
Humans
In Situ Hybridization, Fluorescence
Melanoma-Specific Antigens/genetics
Membrane Proteins/genetics
Oligonucleotide Array Sequence Analysis
Syndrome
Twins
p21-Activated Kinases/genetics

Figure

• 

  Fig. 1. Karyotype of one of the monozygotic twin sisters. The deletion in the long arm of chromosome 3 was apparently a terminal deletion, as shown by the arrow. The karyotype was initially designated 46,XX,del(3)(q29).

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  Fig. 2. Array CGH profile of chromosome 3 in one of the monozygotic twin sisters. X-axis represents the probe index on chromosome 3, and Y-axis represents the signal log2 ratio of the probe. (A) The whole chromosome 3 view showed copy number loss in the 3q29 region. The green dots with log2 value of −1 represent a 1:2 copy number ratio of the test to reference genomic DNA, indicating a heterozygous deletion. (B) The expansion view of the 3q29 region distinctly revealed a 4.0-Mb heterozygous interstitial deletion in the Chr3:195,007,970-199,085,431.

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  Fig. 3. Metaphase fluorescence in situ hybridization (FISH) analysis of one of the monozygotic twin sisters using TelVysion 3q SpectrumOrange probe and TelVysion 3p SpectrumGreen probe (Abbott Molecular Inc., USA). (A) TelVysion 3q deletion was detected (arrow), but 2 TelVysion 3p signals were intact. (B) TelVysion 3q deletion was also identified in the same metaphase with G-banding obtained using 4,6-diamidino-2-phenylindole (DAPI) staining (arrow).

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  Fig. 4. Visualization of the novel deletion region on 3q29 using the University of California Santa Cruz (UCSC) Genome Browser. The UCSC browser shows a 4.0-Mb region (within positions Chr3:195,007,970-199,085,431), encompassing the reference genes, copy number variation regions, and segmental duplications.

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