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学科主题: 临床医学
题名:
ABCB6 Mutations Cause Ocular Coloboma
作者: Wang, Lejing1; He, Fei; Bu, Juan1; Liu, Xiaqi; Du, Wei1; Dong, Jiamei1,2; Cooney, Jeffrey D.3,4; Dubey, Sushi Kumar5; Shi, Yi; Gong, Bo; Li, Jing; McBride, Paul F.3,4; Jia, Yanlei6; Lu, Fang; Soltis, Kathleen A.3,4; Lin, Ying; Namburi, Prasanthi5; Liang, Chen1; Sundaresan, Periasamy5; Paw, Barry H.3,4; Li, Dean Y.7,8,9; Phillips, John D.10; Yang, Zhenglin
刊名: AMERICAN JOURNAL OF HUMAN GENETICS
发表日期: 2012-01-13
DOI: 10.1016/j.ajhg.2011.11.026
卷: 90, 期:1, 页:40-48
收录类别: SCI
文章类型: Article
WOS标题词: Science & Technology
类目[WOS]: Genetics & Heredity
研究领域[WOS]: Genetics & Heredity
关键词[WOS]: CONGENITAL EYE MALFORMATIONS ; CONSECUTIVE BIRTHS ; GENE ; TRANSPORTERS ; ANOPHTHALMIA ; FAMILY ; RESISTANCE ; LOCALIZES ; ANOMALIES ; ANIRIDIA
英文摘要:

Ocular coloboma is a developmental defect of the eye and is due to abnormal or incomplete closure of the optic fissure. This disorder displays genetic and clinical heterogeneity. Using a positional cloning approach, we identified a mutation in the ATP-binding cassette (ABC) transporter ABCB6 in a Chinese family affected by autosomal-dominant coloboma. The Leu811Val mutation was identified in seven affected members of the family and was absent in six unaffected members from three generations. A LOD score of 3.2 at theta = 0 was calculated for the mutation identified in this family. Sequence analysis was performed on the ABCB6 exons from 116 sporadic cases of microphthalmia with coloboma (MAC), isolated coloboma, and aniridia, and an additional mutation (A57T) was identified in three patients with MAC. These two mutations were not present in the ethnically matched control populations. Immunostaining of transiently transfected, Myc-tagged ABCB6 in retinal pigment epithelial (RPE) cells showed that it localized to the endoplasmic reticulum and Golgi apparatus of RPE cells. RT-PCR of ABCB6 mRNA in human cell lines and tissue indicated that ABCB6 is expressed in the retinae and RPE cells. Using zebrafish, we show that abcb6 is expressed in the eye and CNS. Morpholino knockdown of abcb6 in zebrafish produces a phenotype characteristic of coloboma and replicates the clinical phenotype observed in our index cases. The knockdown phenotype can be corrected with coinjection of the wild-type, but not mutant, ABCB6 mRNA, suggesting that the phenotypes observed in zebrafish are due to insufficient abcb6 function. Our results demonstrate that ABCB6 mutations cause ocular coloboma.

语种: 英语
所属项目编号: 81025006 ; 81170883 ; 30470975 ; 30540030 ; 30950007 ; R01 DK070838 ; P01 HL032262 ; DK02503 ; DK083909
项目资助者: National Natural Science Foundation of China ; Department of Science and Technology of Sichuan Province, China ; American Heart Association ; American Society of Hematology ; March of Dimes Foundation ; National Institutes of Health
WOS记录号: WOS:000299409100003
Citation statistics:
内容类型: 期刊论文
URI标识: http://ir.bjmu.edu.cn/handle/400002259/64618
Appears in Collections:北京大学第三临床医学院_眼科_期刊论文

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作者单位: 1.Peking Univ, Hosp 3, Dept Ophthalmol, Beijing 100191, Peoples R China
2.Peking Univ, Hosp 3, Party Sch, Cent Comm Communist Party China, Beijing 100091, Peoples R China
3.Harvard Univ, Brigham & Womens Hosp, Sch Med, Div Hematol, Boston, MA 02115 USA
4.Harvard Univ, Childrens Hosp Boston, Sch Med, Div Hematol Oncol, Boston, MA 02115 USA
5.Aravind Eye Hosp, Aravind Med Res Fdn, Dept Genet, Dr G Venkataswamy Eye Res Inst, Madurai 625020, Tamil Nadu, India
6.Municipal Hosp Zaozhuang, Dept Ophthalmol, Zaozhuang 277102, Shandong, Peoples R China
7.Univ Utah, Sch Med, Program Mol Med, Salt Lake City, UT 84112 USA
8.Univ Utah, Huntsman Canc Inst, Dept Oncol Sci, Salt Lake City, UT 84112 USA
9.Univ Utah, Dept Med, Salt Lake City, UT 84112 USA
10.Univ Utah, Sch Med, Div Hematol, Salt Lake City, UT 84112 USA

Recommended Citation:
Wang, Lejing,He, Fei,Bu, Juan,et al. ABCB6 Mutations Cause Ocular Coloboma[J]. AMERICAN JOURNAL OF HUMAN GENETICS,2012,90(1):40-48.
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