Isolated Vitreoretinal Amyloidosis in the Absence of Transthyretin Mutations

Abstract

Abstract: : Purpose: Vitreoretinal amyloidosis is believed to be associated universally with mutations in the genes encoding transthyretin and found exclusively as part of the familial amyloidotic polyneuropathy (FAP) syndrome. Here we investigate an unusual case of biopsy-proven vitreoretinal amyloidosis without systemic involvement and demonstrate that vitreoretinal amyloidosis can occur with intact wildtype transthyretin genes. Methods: A vitreous biopsy specimen from a 70-year old woman who presented with cloudy vision was stained with hematoxylin, eosin, and Congo red. Genomic DNA was isolated from peripheral blood, and exons encoding the entire transthyretin protein were amplified by the polymerase chain reaction and analyzed by direct DNA sequencing. Results: Histopathologic analysis of the vitreous biopsy revealed eosinophilic lobules that stained positively with Congo red and demonstrated birefringence under polarized light diagnostic of amyloidosis. Genomic DNA sequence analysis demonstrated no mutations in the entire coding sequence of the transthyretin genes. Seven years of clinical follow-up revealed no evidence of systemic disease suggestive of FAP. Conclusions: This study demonstrates that vitreoretinal amyloidosis can occur in the absence of transthyretin mutations. Moreover, these data raise the possibility that isolated vitreoretinal amyloidosis may represent a disorder separate from FAP. We conclude that vitreoretinal amyloidosis encompasses a more heterogeneous group of disorders than has been previously described.

Keywords: vitreous • gene/expression • pathology: human