Hereditary gelsolin amyloidosis – clinical symptoms and molecular genetic cause

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‘ workplace: 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: Cesk Slov Neurol N 2021; 84(5): 449-455
Category: Original Paper
doi: 10.48095/cccsnn2021449


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.


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


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