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学科主题临床医学
ABCB6 Mutations Cause Ocular Coloboma
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
2012-01-13
DOI10.1016/j.ajhg.2011.11.026
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
WOS记录号WOS:000299409100003
引用统计
被引频次:38[WOS]   [WOS记录]     [WOS相关记录]
文献类型期刊论文
条目标识符http://ir.bjmu.edu.cn/handle/400002259/64618
专题北京大学第三临床医学院_眼科
北京大学第二临床医学院_眼科
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
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GB/T 7714
Wang, Lejing,He, Fei,Bu, Juan,et al. ABCB6 Mutations Cause Ocular Coloboma[J]. AMERICAN JOURNAL OF HUMAN GENETICS,2012,90(1):40-48.
APA Wang, Lejing.,He, Fei.,Bu, Juan.,Liu, Xiaqi.,Du, Wei.,...&Yang, Zhenglin.(2012).ABCB6 Mutations Cause Ocular Coloboma.AMERICAN JOURNAL OF HUMAN GENETICS,90(1),40-48.
MLA Wang, Lejing,et al."ABCB6 Mutations Cause Ocular Coloboma".AMERICAN JOURNAL OF HUMAN GENETICS 90.1(2012):40-48.
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