Progressive juvenile-onset punctate cataracts caused by mutation of the γD-crystallin gene

被引:179
作者
Stephan, DA
Gillanders, E
Vanderveen, D
Freas-Lutz, D
Wistow, G
Baxevanis, AD
Robbins, CM
VanAuken, A
Quesenberry, MI
Bailey-Wilson, J
Juo, SHH
Trent, JM
Smith, L
Brownstein, MJ
机构
[1] NIMH, Genet Lab, NHGRI, NIH, Bethesda, MD 20892 USA
[2] NIH, Canc Genet Branch, Natl Human Genome Res Inst, Bethesda, MD 20892 USA
[3] NEI, Sect Mol Struct & Funct, NIH, Bethesda, MD 20892 USA
[4] NIH, Genome Technol Branch, Natl Human Genome Res Inst, Bethesda, MD 20892 USA
[5] Harvard Univ, Sch Med, Dept Ophthalmol, Boston, MA 02115 USA
[6] Childrens Hosp, Boston, MA 02115 USA
[7] NIH, Sect Stat Genet, Ctr Inherited Dis Res, Natl Human Genome Res Inst, Baltimore, MD 21224 USA
关键词
D O I
10.1073/pnas.96.3.1008
中图分类号
O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];
学科分类号
07 ; 0710 ; 09 ;
摘要
Cataracts are a significant public health problem. Here, we describe the genetic alteration responsible far a progressive form of cataract, segregating as an autosomal dominant trait in a three-generation pedigree, Unlike most autosomal dominant cataracts, these are not clinically apparent at birth but are initially observed in the first year or two of life. The opacification evolves relatively slowly, generally necessitating removal of the lens in childhood or early adolescence. A genome-wide search in our kindred revealed linkage at 2q33-35 where the gamma-crystallin gene cluster resides. A single base alteration resulting in an Arg- 14 --> Cys (R14C) substitution in gamma D-crystallin was subsequently identified. Protein modeling suggests that the effect of this mutation is a subtle one, affecting the surface properties of the crystallin molecule rather than its tertiary structure, consistent with the fact that the patients' lenses are normal at birth. This is the first gene defect shown to be responsible for a noncongenital progressive cataract, and studying the defective protein should teach us more about the mechanisms underlying cataract formation.
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页码:1008 / 1012
页数:5
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