Auw-Haedrich Claudia, Agostini Hansjürgen, Clausen Ina, Reinhard Thomas, Eberwein Philipp, Schorderet Daniel F, Gruenauer-Kloevekorn Claudia
University Eye Hospital, Freiburg, Germany.
Ophthalmology. 2009 Jan;116(1):46-51. doi: 10.1016/j.ophtha.2008.08.050. Epub 2008 Nov 18.
To present the light and electron microscopic findings of a unique corneal dystrophy never before described in a German family carrying the Gly623Asp Mutation of the TGFBI gene with late clinical onset.
Experimental study.
Four affected and 6 nonaffected family members.
Slit-lamp examination, photographic documentation, and isolation of genomic DNA from peripheral blood leucocytes obtained from each family member examined. Exons 3, 4, 5, and 11 to 14 of the TGFBI gene were amplified and sequenced in these family members. Five corneal buttons of 3 affected siblings were excised at the time of penetrating keratoplasty. Light and electron microscopic examination were performed including immunohistochemistry with antibodies against keratoepithelin (KE) 2 and 15.
Clinical and histologic characteristics of corneal opacification in affected patients and presence of coding region changes in the TGFBI gene.
The specimens showed destructive changes in Bowman's layer and the adjacent stroma. Patchy Congo red-positive amyloid deposits were found within the epithelium in 1 cornea, in Bowman's layer and in the anterior stroma of all specimens also showing KE2, but not KE15, immunostaining. Electron microscopy revealed deposits mainly located in the anterior stroma and Bowman's layer and in small amounts in the basal area of some epithelial cells. The destroyed areas were strongly Alcian blue-positive, the Masson Trichrome stain proved mainly negative for the deposits. All affected but none of the unaffected family members had a heterozygous missense mutation in exon 14 of the TGFBI gene (G-->A transition at nucleotide 1915) replacing glycin by aspartic acid amino acid (Gly623Asp) at position 623 of the KE protein.
In contrast with the patient carrying the Gly623Asp mutation of the TGFBI gene described by Afshari et al, our cases presented with Salzmann's nodular degeneration-like clinical features and their specimens contained KE2-positive amyloid. The reason for this now "meeting the expectation histologic phenotype" is unclear. The histologic findings emphasize that this is a unique corneal dystrophy, which shares no clinical characteristics with Reis-Bücklers' dystrophy and should be treated as a distinct entity.
FINANCIAL DISCLOSURE(S): The authors have no proprietary or commercial interest in any materials discussed in this article.
呈现一个德国家庭中一种独特角膜营养不良的光镜和电镜检查结果，该角膜营养不良此前从未被描述过，其携带TGFBI基因的Gly623Asp突变且临床发病较晚。
实验研究。
4名患病家庭成员和6名未患病家庭成员。
裂隙灯检查、摄影记录，并从每位接受检查的家庭成员的外周血白细胞中分离基因组DNA。对这些家庭成员的TGFBI基因的第3、4、5和11至14外显子进行扩增和测序。在穿透性角膜移植时，切除3名患病同胞的5个角膜植片。进行光镜和电镜检查，包括用抗角膜上皮素（KE）2和15的抗体进行免疫组织化学检查。
患病患者角膜混浊的临床和组织学特征以及TGFBI基因编码区变化的存在情况。
标本显示Bowman层和相邻基质有破坏性改变。在1个角膜的上皮内、所有标本的Bowman层和前基质中发现了散在的刚果红阳性淀粉样沉积物，这些标本也显示KE2免疫染色，但未显示KE15免疫染色。电镜显示沉积物主要位于前基质和Bowman层，少量存在于一些上皮细胞的基底区域。破坏区域强阿尔辛蓝阳性，Masson三色染色显示沉积物主要为阴性。所有患病家庭成员，但未患病家庭成员均无TGFBI基因第14外显子的杂合错义突变（核苷酸1915处的G→A转换），该突变在KE蛋白的第623位将甘氨酸替换为天冬氨酸（Gly623Asp）。
与Afshari等人描述的携带TGFBI基因Gly623Asp突变的患者不同，我们的病例表现出萨尔茨曼结节状变性样临床特征，其标本含有KE2阳性淀粉样物质。这种现在“符合预期组织学表型”的原因尚不清楚。组织学发现强调这是一种独特的角膜营养不良，与Reis-Bücklers营养不良没有共同的临床特征，应被视为一个独特的实体。
作者对本文讨论的任何材料均无专利或商业利益。
