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Clinical and Histopathological Features of Gelsolin Amyloidosis Associated with a Novel GSN Variant p.Glu580Lys

Authors :
Jože Pižem
Natasa Teran
Ana Fakin
Matteo de Rosa
Marko Hawlina
Michela Bollati
Ana Gornik
Helena Jaklič
Borut Peterlin
Maja Potrč
Marija Volk
Brigita Drnovsek-Olup
Alojzija Hočevar
Vladimir Pfeifer
Katarina Vogelnik
Aleš Maver
Source :
International Journal of Molecular Sciences, Volume 22, Issue 3, International Journal of Molecular Sciences, Vol 22, Iss 1084, p 1084 (2021), International journal of molecular sciences, 22 (2021): 1–15. doi:10.3390/ijms22031084, info:cnr-pdr/source/autori:Potrc M.; Volk M.; de Rosa M.; Pizem J.; Teran N.; Jaklic H.; Maver A.; Drnovsek-Olup B.; Bollati M.; Vogelnik K.; Hocevar A.; Gornik A.; Pfeifer V.; Peterlin B.; Hawlina M.; Fakin A./titolo:Clinical and histopathological features of gelsolin amyloidosis associated with a novel gsn variant p.Glu580lys/doi:10.3390%2Fijms22031084/rivista:International journal of molecular sciences (Print)/anno:2021/pagina_da:1/pagina_a:15/intervallo_pagine:1–15/volume:22, International journal of molecular sciences, vol. 22, no. 3, 1084, 2021.
Publication Year :
2021
Publisher :
MDPI AG, 2021.

Abstract

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.

Details

ISSN :
14220067
Volume :
22
Database :
OpenAIRE
Journal :
International Journal of Molecular Sciences
Accession number :
edsair.doi.dedup.....20bf0c7e808fee9bc7bb3f03502cbd97
Full Text :
https://doi.org/10.3390/ijms22031084