Familial Amyloidosis, Finnish Type
Familial Amyloidosis, Finnish Type | |
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Other names | Gelsolin amyloidosis |
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This condition is inherited in an autosomal dominant manner |
Familial Amyloidosis, Finnish Type (FAF), also called hereditary gelsolin amyloidosis and AGel amyloidosis (AGel), is an amyloid condition with a number of associated cutaneous and neurological presentations deriving from the aberrant proteolysis of a mutated form of plasma gelsolin.[1] First described in 1969 by the Finnish ophthalmologist Jouko Meretoja,[2] FAF is uncommon with 400–600 cases described in Finland and 15 elsewhere.[3]
Clinical presentation
The disorder is primarily associated with eye, skin, and cranial nerve symptoms with the onset of symptoms appearing between the thirties and fifties.[3] The most common characteristic is type II lattice corneal dystrophy with other signs such as polyneuropathy, dermatochalasis, open-angle glaucoma, bilateral progressive facial paralysis, cutis laxa, skin fragility with ecchymosis, facial mask, diffuse hair loss, dry skin, carpal tunnel syndrome, nephrotic syndrome, cardiomyopathy with conduction alterations, and early aging associated with the condition.[3] There are no specific treatments available.
Plasma gelsolin amyloid
Plasma gelsolin is a 755 amino acid, 83 kDa plasma protein involved in the regulation and resolution of inflammation. It is made up of six "gelsolin domains," each consisting of a 5–6 strand β-sheet between one long and one short α-helix.[4] Several single point mutations in the GSN gene will lead to loss of structure in residues 254–258 of the second domain. The misfold and associated increased flexibility opens up a cleavage site to the enzyme furin.[5] Plasma gelsolin is cleaved as it passes through the Golgi before being secreted from the cell. A 68 kDa C-terminal fragment is further endoproteolysed into 5 and 8 kDa fragments that are amyloidogenic.[1]
The most common mutations are D187N/Y (G654A/T on gene GSN, chromosome 9)[6] with additional reports of G167R, N184K, P432R, A551P, and Ala7fs in the medical literature.[7] Mutations are inherited in an autosomal dominant fashion.[8][9]
Names
Many names exist in the scientific literature in reference to this disease including:
- Familial amyloid neuropathy type IV
- Familial amyloidotic polyneuropathy (FAP) type IV
- Lattice corneal dystrophy, gelsolin type
- Lattice corneal dystrophy type 2 (LCD2)
- Meretoja's syndrome
See also
References
- ^ a b Solomon, James P.; Page, Lesley J.; Balch, William E.; Kelly, Jeffery W. (June 2012). "Gelsolin amyloidosis: genetics, biochemistry, pathology and possible strategies for therapeutic intervention". Critical Reviews in Biochemistry and Molecular Biology. 47 (3): 282–296. doi:10.3109/10409238.2012.661401. ISSN 1040-9238. PMC 3337338. PMID 22360545.
- ^ Meretoja, J. (December 1969). "Familial systemic paramyloidosis with lattice dystrophy of the cornea, progressive cranial neuropathy, skin changes and various internal symptoms. A previously unrecognized heritable syndrome". Annals of Clinical Research. 1 (4): 314–324. ISSN 0003-4762. PMID 4313418.
- ^ a b c Friedhofer, Henri; Vassiliadis, Aneta Hionia; Scarpa, Marcela Benetti; Luitgards, Bruno Ferreira; Gemperli, Rolf (2017-12-13). "Meretoja Syndrome: General Considerations and Contributions of Plastic Surgery in Surgical Treatment". Aesthetic Surgery Journal. 38 (1): –10–NP15. doi:10.1093/asj/sjx172. ISSN 1527-330X. PMID 29149274.
- ^ Nag, Shalini; Larsson, Mårten; Robinson, Robert C.; Burtnick, Leslie D. (2013-06-10). "Gelsolin: The tail of a molecular gymnast: Gelsolin Superfamily Proteins". Cytoskeleton. 70 (7): 360–384. doi:10.1002/cm.21117. ISSN 1949-3584. PMID 23749648.
- ^ Kazmirski, Steven L.; Howard, Mark J.; Isaacson, Rivka L.; Fersht, Alan R. (2000-09-26). "Elucidating the mechanism of familial amyloidosis– Finnish type: NMR studies of human gelsolin domain 2". Proceedings of the National Academy of Sciences. 97 (20): 10706–10711. Bibcode:2000PNAS...9710706K. doi:10.1073/pnas.180310097. ISSN 0027-8424. PMC 27087. PMID 10995458.
- ^ Kiuru‐Enari, S.; Keski‐Oja, J.; Haltia, M. (2005). "Cutis laxa in hereditary gelsolin amyloidosis". British Journal of Dermatology. 152 (2): 250–257. doi:10.1111/j.1365-2133.2004.06276.x. ISSN 1365-2133. PMID 15727635. S2CID 26899540.
- ^ Zorgati, Habiba; Larsson, Mårten; Ren, Weitong; Sim, Adelene Y. L.; Gettemans, Jan; Grimes, Jonathan M.; Li, Wenfei; Robinson, Robert C. (2019-07-09). "The role of gelsolin domain 3 in familial amyloidosis (Finnish type)". Proceedings of the National Academy of Sciences. 116 (28): 13958–13963. doi:10.1073/pnas.1902189116. ISSN 0027-8424. PMC 6628662. PMID 31243148.
- ^ Rapini, Ronald P.; Bolognia, Jean L.; Jorizzo, Joseph L. (2007). Dermatology: 2-Volume Set. St. Louis: Mosby. ISBN 978-1-4160-2999-1.
- ^ Ghoshdastider U, Popp D, Burtnick LD, Robinson RC (2013). "The expanding superfamily of gelsolin homology domain proteins". Cytoskeleton. 70 (11): 775–95. doi:10.1002/cm.21149. PMID 24155256. S2CID 205643538.