Mutations in SCO2 Are Associated with Autosomal-Dominant High-Grade Myopia

被引：99

作者：

Tran-Viet, Khanh-Nhat ^{[1
]}

Powell, Caldwell ^{[1
]}

Barathi, Veluchamy A. ^{[2
,3
,4
]}

Klemm, Thomas ^{[2
]}

Maurer-Stroh, Sebastian ^{[5
,6
]}

Limviphuvadh, Vachiranee ^{[5
,6
]}

Soler, Vincent ^{[7
]}

Ho, Candice ^{[3
]}

Yanovitch, Tammy ^{[8
]}

Schneider, Georg ^{[5
,9
]}

Li, Yi-Ju ^{[1
,2
,10
,13
]}

Nading, Erica ^{[1
,11
]}

Metlapally, Ravikanth ^{[12
]}

Saw, Seang-Mei ^{[13
]}

Goh, Liang ^{[2
,13
]}

Rozen, Steve ^{[2
]}

Young, Terri L. ^{[1
,2
,11
,13
]}

机构：

[1] Duke Ctr Human Genet, Durham, NC 27710 USA

[2] Duke Natl Univ Singapore, Grad Sch Med, Singapore 169857, Singapore

[3] Singapore Eye Res Inst, Singapore 168751, Singapore

[4] Natl Univ Singapore, Yong Loo Lin Sch Med, Singapore 119077, Singapore

[5] Agcy Sci Technol & Res, Bioinformat Inst, Matrix 138671, Singapore

[6] Nanyang Technol Univ, Sch Biol Sci, Singapore 637551, Singapore

[7] Univ Toulouse 3, UMRS 563, Ctr Physiopathol Toulouse Purpan, F-31062 Toulouse, France

[8] Univ Oklahoma, Dean McGee Eye Inst, Dept Ophthalmol, Oklahoma City, OK 73104 USA

[9] IST Austria, A-3400 Klosterneuburg, Austria

[10] Duke Univ, Sch Med, Dept Biostat & Bioinformat, Durham, NC 27710 USA

[11] Duke Univ, Ctr Eye, Dept Ophthalmol, Durham, NC 27710 USA

[12] Univ Calif Berkeley, Vis Sci Grp, Sch Optometry & Dept, Berkeley, CA 94720 USA

[13] Natl Univ Singapore, Yong Loo Lin Sch Med, Saw Swee Hock Sch Publ Hlth, Singapore 117597, Singapore

来源：

AMERICAN JOURNAL OF HUMAN GENETICS | 2013年 / 92卷 / 05期

基金：

美国国家卫生研究院; 英国医学研究理事会;

关键词：

BLOOD-RETINAL BARRIER; REFRACTIVE ERRORS; PIGMENT-EPITHELIUM; GENE-EXPRESSION; UNITED-STATES; BLUE-LIGHT; PREVALENCE; CARDIOMYOPATHY; PATHOGENESIS; IMPAIRMENT;

D O I：

10.1016/j.ajhg.2013.04.005

中图分类号：

Q3 [遗传学];

学科分类号：

071007 ; 090102 ;

摘要：

Myopia, or near-sightedness, is an ocular refractive error of unfocused image quality in front of the retinal plane. Individuals with high-grade myopia (dioptric power greater than -6.00) are predisposed to ocular morbidities such as glaucoma, retinal detachment, and myopic maculopathy. Nonsyndromic, high-grade myopia is highly heritable, and to date multiple gene loci have been reported. We performed exome sequencing in 4 individuals from an 11-member family of European descent from the United States. Affected individuals had a mean dioptric spherical equivalent of -22.00 sphere. A premature stop codon mutation c.157C>T (p.Gln53*) cosegregating with disease was discovered within SCO2 that maps to chromosome 22q13.33. Subsequent analyses identified three additional mutations in three highly myopic unrelated individuals (c.341G>A, c.418G>A, and c.776C>T). To determine differential gene expression in a developmental mouse model, we induced myopia by applying a -15.00D lens over one eye. Messenger RNA levels of SCO2 were significantly downregulated in myopic mouse retinae. Immunohistochemistry in mouse eyes confirmed SCO2 protein localization in retina, retinal pigment epithelium, and sclera. SCO2 encodes for a copper homeostasis protein influential in mitochondrial cytochrome c oxidase activity. Copper deficiencies have been linked with photoreceptor loss and myopia with increased scleral wall elasticity. Retinal thinning has been reported with an SCO2 variant. Human mutation identification with support from an induced myopic animal provides biological insights of myopic development.

引用

页码：820 / 826

页数：7

共 63 条

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