The present study demonstrates the first successful in vitro creation of amyloid-like fibrils from Asn187 gelsolin peptides and provides evidence that amyloid formation in Finnish amyloidosis is a direct consequence of the Asp187----Asn substitution in gelsolin.
We report the first known case of a patient who had amyloidosis both due to a mutant transthyretin (p.Val122Ile) and due to a novel variant in the gelsolin gene (p.Ala578Pro).
One patient with transthyretin amyloidosis and 1 patient with gelsolinamyloidosis with no specific mutation identified were diagnosed based on genetic confirmation in their first-degree relative.
The gelsolin gene defect causes expression of variant gelsolin, followed by systemic deposition of gelsolinamyloid (AGel) in HGA patients and even other consequences on the metabolism and function of gelsolin.
We analysed elastic fibre pathology in dermal and vascular tissue and plasma samples from 35 patients with AGelamyloidosis and 40 control subjects by transmission electron microscopy, immunohistochemistry and ELISA methods.
In the disease familial amyloidosis, Finnish type (FAF), also known as AGelamyloidosis (AGel), the mechanism by which point mutations in the calcium-regulated actin-severing protein gelsolin lead to furin cleavage is not understood in the intact protein.
The gelsolin fragments isolated from at least one patient with amyloidosis have been reported to have an amino acid substitution, with asparagine replacing aspartic acid at position 187 of the plasma gelsolin.
To provide a comprehensive review of the types of amyloidosis that can be associated with ocular involvement, the images and clinical descriptions of patients with amyloidosis structurally related to gelsolin, keratoepithelin and lactoferrin were obtained in collaborations with the ophthalmology departments of hospitals in Mainz (Germany) and Helsinki (Finland).<b>Results</b>: Overall, ocular morbidity was detected in 41 of the 178 patients with amyloidosis (23%).
In homozygous FAF (Asn-187), the 65-kd fragment, which contains the amyloid-forming region (Ala173-Met243), and the 55-kd fragment, which is devoid of that region, are the major gelsolin species in plasma; whereas normal gelsolin, as well as a 70-kd fragment identified as the C-terminal portion of gelsolin starting at Glu122, and a 45-kd fragment starting at Ser384, are minor components.
Follow-up of these cases might give us more insight into pathogenicity and potential treatment strategy of this atypical presentation of gelsolinamyloidosis.
The type of amyloidosis was AL in 51 patients (55.4%), non-V30M mutant ATTR in 10 (10.9%), V30M mutant ATTR in 8 (8.7%), serum amyloid A-derived amyloidosis (AA) in 6 (6.5%), wild-type ATTR in 4 (4.3%), gelsolin in 3 (3.3%), and unclassified in 10 (10.9%).