Annals of Laboratory Medicine

Korean Society for Laboratory Medicine (대한진단검사의학회)
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Identification of a Novel Deletion Region in 3q29 Microdeletion Syndrome by Oligonucleotide Array Comparative Genomic Hybridization

Seo, Eul-Ju;Jun, Kyung-Ran;Yoo, Han-Wook;Yoo, Hanik-K.;Lee, Jin-Ok

  • Published : 20100000
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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.

배경 : 3q29 미세결손 증후군은 정신지연과 발달지연, 작은 머리증, 정상 또는 경한 이상형태증을 가지는 유전체 질환이며, 대부분의 경우 low-copy repeats (LCRs) 사이에서 1.6 Mb의 전형적인 결손을 보인다. 본 연구에서는 특이한 임상소견을 동반한 일란성쌍둥이 자매에서 oligonucleotide array CGH를 통하여 4.0 Mb의 새로운 3q29 미세결손을 확인하였다. 방법 : G-분염법의 염색체 검사를 자매와 부모에서 시행하였고, Human Whole Genome 244K CGH oligonucleotide microarray (Agilent Technologies, USA)를 사용하여 얻어진 고해상도 array CGH의 유전체 변이를 FISH 분석으로 검증하였으며, 그 결과를 유전체 데이터베이스 자원을 이용하여 분석하였다. 결과 : 두 자매 모두 G-분염법에서 de novo 46,XX,del(3)(q29) 핵형을 보였다. Array CGH에서는 3q29의 4.0 Mb 중간 결손을 나타내었으며, 이 결손 부위에는 39개의 유전자가 있고 결손의 경계 부위에서 LCRs는 관찰되지 않았다. 자매는 3q29 미세결손 증후군의 공통 소견 외에 주의력부족행동과다장애와 사시, 심장기형, 흰머리 등의 소견이 추가적으로 관찰되었다. 정신지연에 중요한 역할을 하는 것으로 알려진 PAK2와 DLG1 이외에, HES1 과 MFI2가 사시, 심장기형, 흰머리의 후보 유전자일 가능성이 있다. 결론 : 일란성쌍둥이 자매에서 관찰된 3q29 미세결손은 전형적인 1.6 Mb 결손을 포함한 새로운 부위의 4.0 Mb 결손이었으며, 유전체 재배열은 비대립동종재조합이 아닌 다른 기전에 의한 것으로 추정된다. 각 유전자와 표현형과의 연관을 규명하기 위해서 분자유전학적 기능 연구가 필요하다.

Keywords

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