H626R TGFBI变异型格子状营养不良中的球形变性：多模态分析

Spheroidal degeneration in H626R TGFBI variant lattice dystrophy: a multimodality analysis.

作者信息

Lai Kevin, Reidy Jason, Bert Benjamin, Milman Tatyana

机构信息

*Department of Ophthalmology, The New York Eye and Ear Infirmary, New York, NY; †Department of Pathology, Electron Microscopy Laboratory, Beth Israel Medical Center, New York, NY; ‡Department of Ophthalmology, University of California, San Francisco, CA; and §Department of Pathology and Laboratory Medicine, The New York Eye and Ear Infirmary, New York, NY.

出版信息

Cornea. 2014 Jul;33(7):726-32. doi: 10.1097/ICO.0000000000000140.

DOI:10.1097/ICO.0000000000000140

PMID:24831201

Abstract

PURPOSE

The aim of this study was to describe clinical, imaging, molecular genetic, histopathologic, immunohistochemical, and ultrastructural characteristics of coexistent amyloid and spheroidal degeneration-type deposits in a family with histidine-626-arginine transforming growth factor beta-induced (H626R TGFBI) variant lattice dystrophy.

METHODS

This is a retrospective clinical-pathological and genetic analysis of one family with H626R variant lattice dystrophy.

RESULTS

Pedigree analysis showed an autosomal dominant inheritance pattern of the disease. Examination of 3 affected family members revealed asymmetric, thick, branching lattice-like deposits associated with corneal haze. Sequencing of the TGFBI gene revealed a high-penetrance disease-causing sequence variation (H626R CAT>CGT heterozygous). Optical coherence tomography demonstrated fusiform, poorly demarcated hyperechoic stromal deposits with focal hypoechoic central regions. Histology of the corneal discs from 2 affected family members showed stromal deposits consistent with TGFBI amyloid. Some amyloid deposits contained a central nidus of spheroidal degeneration-type material that demonstrated autofluorescence, stained with elastic and Masson trichrome stains, did not stain with periodic acid-Schiff or Congo red stains, was nonbirefringent, and did not immunoreact with keratoepithelin antibodies. Transmission electron microscopy confirmed the presence of amyloid fibrils with central, electrodense, homogeneous, discrete, spheroidal degeneration-type deposits.

CONCLUSIONS

The presence of spheroidal deposits in a subset of affected patients, variability in presentation within an individual and between family members, predominant anterior corneal stromal location and nonimmunoreactivity of deposits for keratoepithelin suggest that these deposits are degenerative in nature. The deposits may arise from ultraviolet light-altered proteins diffused from the limbus, which form a nidus for keratoepithelin deposition.

摘要

目的

本研究旨在描述一个携带组氨酸-626-精氨酸转化生长因子β诱导（H626R TGFBI）变异型格子状营养不良的家族中同时存在的淀粉样变性和球状变性型沉积物的临床、影像学、分子遗传学、组织病理学、免疫组织化学及超微结构特征。

方法

这是一项对一个患有H626R变异型格子状营养不良家族的回顾性临床病理及遗传学分析。

结果

系谱分析显示该疾病为常染色体显性遗传模式。对3名受影响的家族成员进行检查发现，角膜混浊伴有不对称、增厚、分支状的格子样沉积物。TGFBI基因测序显示存在一个高 penetrance 的致病序列变异（H626R CAT>CGT 杂合）。光学相干断层扫描显示梭形、边界不清的高回声基质沉积物，中央区域有局灶性低回声。对2名受影响家族成员的角膜切片进行组织学检查显示，基质沉积物与TGFBI淀粉样变性一致。一些淀粉样沉积物含有球状变性型物质的中央核心，该核心显示自发荧光，用弹性和Masson三色染色法染色，不被过碘酸-希夫或刚果红染色，无双折射，且不与角膜上皮素抗体发生免疫反应。透射电子显微镜证实存在淀粉样原纤维，伴有中央、电子致密、均匀、离散的球状变性型沉积物。