The GSN gene at 9q33.2 codes for the 782 amino acid protein gelsolin. This is a calcium-regulated, actin-modulating protein that binds to the barbed (plus) ends of actin filaments, preventing monomer exchange by end-blocking (capping). Gelsolin also promotes the assembly of actin monomers into filaments (nucleation). It plays a role in ciliogenesis.
Abnormal variants cause AGel amyloidosis. This is suggested by the presence of:
The amyloidosis often causes peripheral neuropathy or CNS manifestations. A typical presentation of the cranial neuropathy phenotype might be involuntary facial twitching, progressive bilateral facial weakness, and tongue atrophy such has been reported with the p.D214Y mutation but other diverse presentations such as with ataxia are possible. Severe systemic disease can develop with amyloid cardiomyopathy, and nephrotic syndrome. The renal involvement appears confined to the p.G194R and p.N211K mutations. The other described mutation causing amyloidosis is p.D214N.
Some polymorphisms are associated with risk of malignancy
- ↑ Park KJ, Park JH, Park JH, Cho EB, Kim BJ, Kim JW. The First Korean Family With Hereditary Gelsolin Amyloidosis Caused by p.D214Y Mutation in the GSN Gene. Annals of laboratory medicine. 2016 May; 36(3):259-62.(Link to article – subscription may be required.)
- ↑ Rowczenio D, Tennent GA, Gilbertson J, Lachmann HJ, Hutt DF, Bybee A, Hawkins PN, Gillmore JD. Clinical characteristics and SAP scintigraphic findings in 10 patients with AGel amyloidosis. Amyloid : the international journal of experimental and clinical investigation : the official journal of the International Society of Amyloidosis. 2014 Dec; 21(4):276-81.(Link to article – subscription may be required.)
- ↑ Yang XD, Zhao SF, Zhang Q, Li W, Wang YX, Hong XW, Hu QG. Gelsolin rs1078305 and rs10818524 polymorphisms were associated with risk of oral squamous cell carcinoma in a Chinese Han population. Biomarkers : biochemical indicators of exposure, response, and susceptibility to chemicals. 2016 May; 21(3):267-71.(Link to article – subscription may be required.)