Department of Ophthalmology, Faculty of Medical and Health Sciences, National Eye Centre, University of Auckland, Auckland, New Zealand.
Br J Ophthalmol. 2010 Jul;94(7):836-42. doi: 10.1136/bjo.2009.159632. Epub 2009 Nov 30.
The corneal dystrophies represent a group of clinically and genetically heterogeneous, inherited diseases, often resulting in bilateral opacification of the cornea, and may require penetrating keratoplasty. Mutations in the transforming growth factor beta-induced (TGFBI) gene segregate with a wide range of phenotypically heterogeneous corneal dystrophies. Many of the other dystrophies remain without molecular characterisation. This study aimed to characterise the molecular basis for corneal disease in a New Zealand population.
Nineteen unrelated individuals affected with a corneal dystrophy (granular, fleck, lattice, posterior polymorphous) and their family members were recruited, a pedigree obtained and their dystrophy extensively phenotyped. After informed consent, samples were taken for DNA extraction. PCR and sequencing of all coding exons of TGFBI was undertaken.
All five patients with granular dystrophy had the R555W mutation, and H626P was identified in an intermediate dystrophy of Bowman layer pedigree. No other mutations were detected including in the stromal dystrophy cases.
Mutational analysis of TGFBI in a small population has identified sequence changes consistent with previously identified genotype-phenotype correlations. A new genotype-phenotype association was also characterised. No mutations were identified in some individuals/pedigrees suggesting greater genetic heterogeneity than is currently known in this group of disorders.
角膜营养不良是一组临床和遗传上具有异质性的遗传性疾病，常导致角膜双侧混浊，可能需要穿透性角膜移植。转化生长因子β诱导（TGFBI）基因突变与广泛的表型异质性角膜营养不良相关。许多其他的营养不良仍然没有分子特征。本研究旨在探讨新西兰人群角膜疾病的分子基础。
招募了 19 名患有角膜营养不良（颗粒状、斑状、格子状、后多形性）的无关个体及其家庭成员，获得了家系图谱，并对其进行了广泛的表型分析。在获得知情同意后，采集样本进行 DNA 提取。对 TGFBI 的所有编码外显子进行 PCR 和测序。
所有 5 名颗粒状营养不良患者均携带 R555W 突变，Bowman 层中间型营养不良家系中发现 H626P 突变。未发现其他突变，包括基质营养不良病例。
对一小部分人群的 TGFBI 进行突变分析，发现了与先前确定的基因型-表型相关性一致的序列变化。还描述了一种新的基因型-表型关联。在一些个体/家系中未发现突变，这表明该组疾病的遗传异质性比目前已知的更大。
