[Identification of a novel deletion region in 3q29 microdeletion syndrome by oligonucleotide array comparative genomic hybridization].
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.
Seo
Eul-Ju
EJ
Department of Laboratory Medicine, University of Ulsan College of Medicine and Asan Medical Center, Seoul 138-736, Korea. ejseo@amc.seoul.kr
Jun
Kyung Ran
KR
Yoo
Han-Wook
HW
Yoo
Hanik K
HK
Lee
Jin-Ok
JO
D048868:Adaptor Proteins, Signal Transducing / Q000235:genetics; D000293:Adolescent; D001289:Attention Deficit Disorder with Hyperactivity / Q000235:genetics; D051792:Basic Helix-Loop-Helix Proteins / Q000235:genetics; D002872:Chromosome Deletion; D025063:Chromosome Disorders / Q000235:genetics*; D002893:Chromosomes, Human, Pair 3; D055028:Comparative Genomic Hybridization / Q000379:methods*; D000074288:Discs Large Homolog 1 Protein; D004200:Diseases in Twins / Q000235:genetics*; D005260:Female; D018398:Homeodomain Proteins / Q000235:genetics; D006801:Humans; D017404:In Situ Hybridization, Fluorescence; D058950:Melanoma-Specific Antigens / Q000235:genetics; D008565:Membrane Proteins / Q000235:genetics; D020411:Oligonucleotide Array Sequence Analysis; D013577:Syndrome; D000072056:Transcription Factor HES-1; D014427:Twins; D054462:p21-Activated Kinases / Q000235:genetics
D048868:Adaptor Proteins, Signal Transducing; D051792:Basic Helix-Loop-Helix Proteins; D000074288:Discs Large Homolog 1 Protein; D018398:Homeodomain Proteins; D058950:Melanoma-Specific Antigens; D008565:Membrane Proteins; D000072056:Transcription Factor HES-1; D054462:p21-Activated Kinases; C513314:DLG1 protein, human; C078493:HES1 protein, human; C515907:PAK2 protein, human