Hereditary gelsolin amyloidosis – clinical symptoms and molecular genetic cause

Česká verzia

Authors: P. Skalická ^1,2; Ľ. Ďuďáková ²; A. Klímová ¹; L. Huňa ¹; C. J. Evans ³; M. Forgáč ⁴; O. Ulmanová ⁴; P. Mečíř ⁴; T. Paleček ⁵; V. Bednářová ⁶; V. Skovajsa ⁷; V. Skalníková ⁸; P. Lišková ^1,2
Authors place of work: Oční klinika 1. LF UK a VFN v Praze ¹; Laboratoř pro studium vzácných nemocí, Klinika pediatrie a dědičných poruch metabolismu 1. LF UK a VFN v Praze ²; UCL Institute of Ophthalmology, Londýn, Velká Británie ³; Neurologická klinika a Centrum klinických neurověd, 1. LF UK a VFN v Praze ⁴; II. interní klinika kardiologie a angiologie 1. LF UK a VFN v Praze ⁵; Klinika nefrologie 1. LF UK a VFN v Praze ⁶; Neurologie, Nemocnice Na Homolce, Praha ⁷; Kardiologie, Nemocnice Na Homolce, Praha ⁸
Published in the journal: Cesk Slov Neurol N 2021; 84(5): 449-455
Category: Original Paper
doi: https://doi.org/10.48095/cccsnn2021449

Summary

Aim: The aim of this study was to describe the clinical findings and molecular genetic cause of hereditary gelsolin amyloidosis in a family of Czech origin and a proband of Slovak origin. Patients and methods: Study participants underwent ophthalmic, neurological, nephrological, and cardiological examination. Sanger sequencing was used to screen the gelsolin gene (GSN). Results: Two mutations previously reported to be associated with hereditary gelsolin amyloidosis were identified; c.640G>T p. (Asp214Tyr) in a heterozygous state was found in seven individuals of Czech origin and c.640G>A p. (Asp214Asn) in the proband of Slovak origin. Linear corneal deposits were observed in the majority of affected subjects with the exception of two men aged 24 and 14 years. In addition to corneal deposits, patients in their fourth decade of life had drooping eyelids and carpal tunnel syndrome. Two oldest patients, aged 65 and 68 years, had also other typical signs of gelsolin amyloidosis, including dry eye syndrome, cutis laxa, and facial nerve lesion. The 68-year-old subject also had severe polyneuropathy, ataxia, dysarthria, and arrhythmia necessitating pacemaker implantation. Conclusion: Hereditary gelsolin amyloidosis should be included in the differential diagnosis of neuropathies and amyloidosis of unknown etiology. Since amyloid deposition in the cornea is easily detectable, ophthalmic examination has a crucial role in the diagnosis of this disease.

Keywords:

polyneuropathy – hereditary gelsolin amyloidosis – linear corneal deposits – facial nerve lesion

Zdroje

1. Maury CP. Homozygous familial amyloidosis, Finnish type: demonstration of glomerular gelsolin-derived amyloid and non-amyloid tubular gelsolin. Clin Nephrol 1993; 40 (1): 53–56.

2. Nikoskinen T, Schmidt EK, Strbian D et al. Natural course of Finnish gelsolin amyloidosis. Ann Med 2015; 47 (6): 506–511. doi: 10.3109/07853890.2015.1075 063.

3. Liskova P, Klintworth GK, Bowling BL et al. Phenotype associated with the H626P mutation and other changes in the TGFBI gene in Czech families. Ophthalmic Res 2008; 40 (2): 105–108. doi: 10.1159/000115325.

4. Evans CJ, Davidson AE, Carnt N et al. Genotype-phenotype correlation for TGFBI corneal dystrophies identifies p. (G623D) as a novel cause of epithelial basement membrane dystrophy. Invest Ophthalmol Vis Sci 2016; 57 (13): 5407–5414. doi: 10.1167/iovs.16-19818.

5. Makioka K, Ikeda M, Ikeda Y et al. Familial amyloid polyneuropathy (Finnish type) presenting multiple cranial nerve deficits with carpal tunnel syndrome and orthostatic hypotension. Neurol Res 2010; 32 (5): 472–475. doi: 10.1179/174313209X409007.

6. Tanskanen M, Paetau A, Salonen O et al. Severe ataxia with neuropathy in hereditary gelsolin amyloidosis: a case report. Amyloid 2007; 14 (1): 89–95. doi: 10.1080/13506120601116393.

7. Kiuru S, Salonen O, Haltia M. Gelsolin-related spinal and cerebral amyloid angiopathy. Ann Neurol 1999; 45 (3): 305–311. doi: 10.1002/1531-8249 (199903) 45: 3<305:: aid-ana5>3.0.co; 2-e.

8. Kiuru S, Javela K, Somer H et al. Altered platelet shape change in hereditary gelsolin Asp187Asn-related amyloidosis. Thromb Haemost 2000; 83 (3): 491–495.

9. Bucki R, Kulakowska A, Byfield FJ et al. Plasma gelsolin modulates cellular response to sphingosine 1-phosphate. Am J Physiol Cell Physiol 2010; 299 (6): C1516–1523. doi: 10.1152/ajpcell.00051.2010.

10. Sun HQ, Yamamoto M, Mejillano M et al. Gelsolin, a multifunctional actin regulatory protein. J Biol Chem 1999; 274 (47): 33179–33182. doi: 10.1074/jbc.274.47.33179.

11. Kwiatkowski DJ. Functions of gelsolin: motility, signaling, apoptosis, cancer. Curr Opin Cell Biol 1999; 11 (1): 103–108. doi: 10.1016/s0955-0674 (99) 80012-x.

12. de la Chapelle A, Tolvanen R, Boysen G et al. Gelsolin-derived familial amyloidosis caused by asparagine or tyrosine substitution for aspartic acid at residue 187. Nat Genet 1992; 2 (2): 157–160. doi: 10.1016/s0955-0674 (99) 80012-x.

13. Kivela T, Tarkkanen A, Frangione B et al. Ocular amyloid deposition in familial amyloidosis, Finnish: an analysis of native and variant gelsolin in Meretoja‘s syndrome. Invest Ophthalmol Vis Sci 1994; 35 (10): 3759–3769.

14. Stewart HS, Parveen R, Ridgway AE et al. Late onset lattice corneal dystrophy with systemic familial amyloidosis, amyloidosis V, in an English family. Br J Ophthalmol 2000; 84 (4): 390–394. doi: 10.1136/bjo.84.4.390.

15. Conceicao I, Sales-Luis ML, De Carvalho M et al. Gelsolin-related familial amyloidosis, Finnish type, in a Portuguese family: clinical and neurophysiological studies. Muscle Nerve 2003; 28 (6): 715–721. doi: 10.1002/mus. 10474.

16. Casal I, Monteiro S, Abreu C et al. Meretoja‘s syndrome: lattice corneal dystrophy, gelsolin type. Case Rep Med 2017; 2017: 2843417. doi: 10.1155/2017/2843417.

17. Huerva V, Velasco A, Sanchez MC et al. Lattice corneal dystrophy type II: clinical, pathologic, and molecular study in a Spanish family. Eur J Ophthalmol 2007; 17 (3): 424–429. doi: 10.1177/112067210701700326.

18. Sunada Y, Shimizu T, Nakase H et al. Inherited amyloid polyneuropathy type IV (gelsolin variant) in a Japanese family. Ann Neurol 1993; 33 (1): 57–62. doi: 10.1002/ana.410330110.

19. Ikeda M, Mizushima K, Fujita Y et al. Familial amyloid polyneuropathy (Finnish type) in a Japanese family: clinical features and immunocytochemical studies. J Neurol Sci 2007; 252 (1): 4–8. doi: 10.1016/j.jns.2006.09.022

20. Ardalan MR, Shoja MM, Kiuru-Enari S. Amyloidosis-related nephrotic syndrome due to a G654A gelsolin mutation: the first report from the Middle East. Nephrol Dial Transplant 2007; 22 (1): 272–275. doi: 10.1093/ndt/gfl548.

21. Gonzalez-Rodriguez J, Ramirez-Miranda A, Hernandez-Da Mota SE et al. TGFBI, CHST6, and GSN gene analysis in Mexican patients with stromal corneal dystrophies. Graefes Arch Clin Exp Ophthalmol 2014; 252 (8): 1267–1272. doi: 10.1007/s00417-014-2648-9.

22. Gorevic PD, Munoz PC, Gorgone G et al. Amyloidosis due to a mutation of the gelsolin gene in an American family with lattice corneal dystrophy type II. N Engl J Med 1991; 325 (25): 1780–1785. doi: 10.1056/NEJM 199112193252505.

23. de la Chapelle A, Kere J, Sack GH Jr. et al. Familial amyloidosis, Finnish type: G654 a mutation of the gelsolin gene in Finnish families and an unrelated American family. Genomics 1992; 13 (3): 898–901. doi: 10.1016/0888-7543 (92) 90182-r.

24. Klaus E, Freyberger E, Kavka G et al. Familial occurrence of a bulbar paralytic form of amyotropic lateral sclerosis with reticular corneal dystrophy and cutis hyperelastica in 3 sisters. Psychiatr Neurol (Basel) 1959; 138: 79–97.

25. Park KJ, Park JH, Park JH et al. The first Korean family with hereditary gelsolin amyloidosis caused by p.D214Y mutation in the GSN Gene. Ann Lab Med 2016; 36 (3): 259–262. doi: 10.3343/alm.2016.36.3.259.

26. Chastan N, Baert-Desurmont S, Saugier-Veber P et al. Cardiac conduction alterations in a French family with amyloidosis of the Finnish type with the p.Asp187Tyr mutation in the GSN gene. Muscle Nerve 2006; 33 (1): 113–119. doi: 10.1002/mus.20448.

27. Solari HP, Ventura MP, Antecka E et al. Danish type gelsolin-related amyloidosis in a Brazilian family: case reports. Arq Bras Oftalmol 2011; 74 (4): 286–288. doi: 10.1590/s0004-27492011000400012.

28. Cabral-Macias J, Garcia-Montano LA, Perezpena-Diazconti M et al. Clinical, histopathological, and in silico pathogenicity analyses in a pedigree with familial amyloidosis of the Finnish type (Meretoja syndrome) caused by a novel gelsolin mutation. Mol Vis 2020; 26: 345–354.

29. Mattila JS, Krootila K, Kivela T et al. Penetrating keratoplasty for corneal amyloidosis in familial amyloidosis, Finnish type. Ophthalmology 2015; 122 (3): 457–463. doi: 10.1016/j.ophtha.2014.09.035.

30. Bradshaw PJ, Stobie P, Knuiman MW et al. Trends in the incidence and prevalence of cardiac pacemaker insertions in an ageing population. Open Heart 2014; 1 (1): e000177. doi: 10.1016/j.ophtha.2014.09.035.

31. McKenna WJ, Maron BJ, Thiene G. Classification, epidemiology, and global burden of cardiomyopathies. Circ Res 2017; 121 (7): 722–730. doi: 10.1161/CIRCRESAHA.117.309711.

32. Schmidt EK, Atula S, Tanskanen M et al. Causes of death and life span in Finnish gelsolin amyloidosis. Ann Med 2016; 48 (5): 352–358. doi: 10.1080/07853890.2016.1177197.

33. Meretoja J. Genetic aspects of familial amyloidosis with corneal lattice dystrophy and cranial neuropathy. Clin Genet 1973; 4 (3): 173–185. doi: 10.1111/j.1399-0004.1973.tb01140.x.

34. Maury CP, Kere J, Tolvanen R et al. Homozygosity for the Asn187 gelsolin mutation in Finnish-type familial amyloidosis is associated with severe renal disease. Genomics 1992; 13 (3): 902–903. doi: 10.1016/0014-5793 (90) 80072-q.