20.500.12556/RUL-134888 Clinical and histopathological features of gelsolin amyloidosis associated with a novel GSN variant p.Glu580Lys Gelsolin amyloidosis typically presents with corneal lattice dystrophy and is most frequently associated with pathogenic GSN variant p.Asp214Asn. Here we report clinical and histopathological features of gelsolin amyloidosis associated with a novel GSN variant p.Glu580Lys. We studied DNA samples of seven members of a two-generation family. Exome sequencing was performed in the proband, and targeted Sanger sequencing in the others. The heterozygous GSN variant p.Glu580Lys was identified in six patients. The patients exhibited corneal dystrophy (5/6), loose skin (5/6) and/or heart arrhythmia (3/6) and one presented with bilateral optic neuropathy. The impact of the mutation on the protein structure was evaluated in silico. The substitution is located in the fifth domain of gelsolin protein, homologous to the second domain harboring the most common pathogenic variant p.Asp214Asn. Structural investigation revealed that the mutation might affect protein folding. Histopathological analysis showed amyloid deposits in the skin. The p.Glu580Lys is associated with corneal dystrophy, strengthening the association of the fifth domain of gelsolin protein with the typical amyloidosis phenotype. Furthermore, optic neuropathy may be related to the disease and is essential to identify before discussing corneal transplantation. gelsolin amyloidosis Meretoja syndrome GSN cutis laxa heart arrhythmia lattice corneal dystrophy optic neuropathy optical coherence tomography true false true Angleški jezik Ni določen Članek v reviji 2022-02-10 10:58:56 2022-02-10 10:58:56 2022-09-14 04:10:30 0000-00-00 00:00:00 2021 0 0 15 str. iss. 3, art. 1084 Vol. 22 2021 0000-00-00 Zaloznikova Objavljeno NiDoloceno 0000-00-00 0000-00-00 0000-00-00 617.7 1422-0067 10.3390/ijms22031084 49715203 RAZ_Potrc_Maja_2021.pdf RAZ_Potrc_Maja_2021.pdf 1 95CEBEB7AF21089B4E606743A816EB39 16f79bc2c435b03132f5d6856793205c525729ef8403ee291e632b1698b5b0ec 15973c32-8a58-11ec-abdb-00155dcfd717 https://repozitorij.uni-lj.si/Dokument.php?lang=slv&id=153614 https://www.mdpi.com/1422-0067/22/3/1084 0 edad3f0d-8a57-11ec-abdb-00155dcfd717 https://repozitorij.uni-lj.si/Dokument.php?lang=slv&id=153613 Medicinska fakulteta 0 0 0