Familial Amyloidosis, Finnish Type

The disorder is primarily associated with eye, skin, and cranial nerve symptoms with the onset of symptoms appearing between the thirties and fifties.

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.

There are no specific treatments available.{{cn|date=December 2024}}

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.{{Cite journal| doi = 10.1002/cm.21117| issn = 1949-3584| volume = 70| issue = 7| pages = 360–384| last1 = Nag| first1 = Shalini| last2 = Larsson| first2 = Mårten| last3 = Robinson| first3 = Robert C.| last4 = Burtnick| first4 = Leslie D.| title = Gelsolin: The tail of a molecular gymnast: Gelsolin Superfamily Proteins| journal = Cytoskeleton| date = 2013-06-10| pmid = 23749648| doi-access = free}}

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.{{Cite journal| doi = 10.1073/pnas.180310097| issn = 0027-8424| volume = 97| issue = 20| pages = 10706–10711| last1 = Kazmirski| first1 = Steven L.| last2 = Howard| first2 = Mark J.| last3 = Isaacson| first3 = Rivka L.| last4 = Fersht| first4 = Alan R.| title = Elucidating the mechanism of familial amyloidosis– Finnish type: NMR studies of human gelsolin domain 2| journal = Proceedings of the National Academy of Sciences| date = 2000-09-26| pmid = 10995458| pmc = 27087| bibcode = 2000PNAS...9710706K| doi-access = free}}

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.

The most common mutations are D187N/Y (G654A/T on gene GSN, chromosome 9){{Cite journal| doi = 10.1111/j.1365-2133.2004.06276.x| issn = 1365-2133| volume = 152| issue = 2| pages = 250–257| last1 = Kiuru‐Enari| first1 = S.| last2 = Keski‐Oja| first2 = J.| last3 = Haltia| first3 = M.| title = Cutis laxa in hereditary gelsolin amyloidosis| journal = British Journal of Dermatology| date = 2005| pmid = 15727635| s2cid = 26899540}} with additional reports of G167R, N184K, P432R, A551P, and Ala7fs in the medical literature.{{Cite journal| doi = 10.1073/pnas.1902189116| issn = 0027-8424| volume = 116| issue = 28| pages = 13958–13963| last1 = Zorgati| first1 = Habiba| last2 = Larsson| first2 = Mårten| last3 = Ren| first3 = Weitong| last4 = Sim| first4 = Adelene Y. L.| last5 = Gettemans| first5 = Jan| last6 = Grimes| first6 = Jonathan M.| last7 = Li| first7 = Wenfei| last8 = Robinson| first8 = Robert C.| title = The role of gelsolin domain 3 in familial amyloidosis (Finnish type)| journal = Proceedings of the National Academy of Sciences| date = 2019-07-09| pmid = 31243148| pmc = 6628662| doi-access = free}}

Mutations are inherited in an autosomal dominant fashion.{{cite book |author=Rapini, Ronald P. |author2=Bolognia, Jean L. |author3=Jorizzo, Joseph L. |title=Dermatology: 2-Volume Set |publisher=Mosby |location=St. Louis |year=2007 |isbn=978-1-4160-2999-1 }}{{cite journal | vauthors = Ghoshdastider U, Popp D, Burtnick LD, Robinson RC | title = The expanding superfamily of gelsolin homology domain proteins | journal = Cytoskeleton | volume = 70 | issue = 11 | pages = 775–95 | year = 2013 | pmid = 24155256 | doi = 10.1002/cm.21149 | s2cid = 205643538 }}

Many names exist in the scientific literature in reference to this disease including:{{cn|date=December 2024}}

• 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

• Wrinkly skin syndrome
• List of cutaneous conditions
• Finnish heritage disease
• Plasma gelsolin

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| OMIM = 105120

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Category:Amyloidosis

Category:Skin conditions resulting from errors in metabolism