Mackey D A, Hewitt A W, Ruddle J B, Vote B, Buttery R G, Toomes C, Metlapally R, Li Y J, Tran-Viet K N, Malecaze F, Calvas P, Rosenberg T, Guggenheim J A, Young T L
Centre for Ophthalmology and Visual Science, University of Western Australia, Lions Eye Institute, Perth, Australia.
Mol Vis. 2011;17:2118-28. Epub 2011 Aug 10.
To describe an Australian pedigree of European descent with a variable autosomal dominant phenotype of: pediatric cortical cataract (CC), asymmetric myopia with astigmatism, familial exudative vitreoretinopathy (FEVR), and primary open-angle glaucoma (POAG).
Probands with CC, FEVR, and POAG were enrolled in three independent genetic eye studies in Tasmania. Genealogy confirmed these individuals were closely related and subsequent examination revealed 11 other family members with some or all of the associated disorders.
Twelve individuals had CC thought to be of childhood onset, with one child demonstrating progressive lenticular opacification. One individual had severe retinal detachment while five others had dragged retinal vessels. Seven individuals had POAG. Seven individuals had myopia in at least one eye ≤-3 Diopters. DNA testing excluded mutations in myocilin, trabecular meshwork inducible glucocorticoid response (MYOC) and tetraspanin 12 (TSPAN12). Haplotype analysis excluded frizzled family receptor 4 (FZD4) and low density lipoprotein receptor-related protein 5 (LRP5), but only partly excluded EVR3. Multipoint linkage analysis revealed multiple chromosomal single-nucleotide polymorphisms (SNPs) of interest, but no statistically significant focal localization.
This unusual clustering of ophthalmic diseases suggests a possible single genetic cause for an apparently new cataract syndrome. This family's clinical ocular features may reflect the interplay between retinal disease with lenticular changes and axial length in the development of myopia and glaucoma.
描述一个具有欧洲血统的澳大利亚家系，其具有可变的常染色体显性表型，包括：小儿皮质性白内障（CC）、伴有散光的不对称性近视、家族性渗出性玻璃体视网膜病变（FEVR）和原发性开角型青光眼（POAG）。
患有CC、FEVR和POAG的先证者被纳入塔斯马尼亚的三项独立遗传性眼病研究。系谱证实这些个体密切相关，随后的检查发现另外11名家庭成员患有部分或全部相关疾病。
12名个体患有被认为是儿童期发病的CC，其中一名儿童表现为进行性晶状体混浊。一名个体发生严重视网膜脱离，另外五名个体有视网膜血管牵拉。7名个体患有POAG。7名个体至少一只眼睛近视度数≤-3屈光度。DNA检测排除了肌纤蛋白、小梁网诱导糖皮质激素反应（MYOC）和四跨膜蛋白12（TSPAN12）中的突变。单倍型分析排除了卷曲蛋白家族受体4（FZD4）和低密度脂蛋白受体相关蛋白5（LRP5），但仅部分排除了EVR3。多点连锁分析揭示了多个感兴趣的染色体单核苷酸多态性（SNP），但没有统计学上显著的局灶定位。
这种不寻常的眼科疾病聚集提示一种明显新的白内障综合征可能存在单一遗传病因。这个家族的临床眼部特征可能反映了视网膜疾病与晶状体变化以及近视和青光眼发展过程中眼轴长度之间的相互作用。
