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Clinical and Histopathological Features of Gelsolin Amyloidosis Associated with a Novel GSN Variant p.Glu580Lys
SIMPLE SUMMARY: Gelsolin amyloidosis is a rare autosomal dominant genetic disease, which typically affects the cornea, skin and sometimes other organ systems and is caused by mutations in a gene coding for gelsolin protein (GSN). We describe a novel mutation of GSN gene, p.Glu580Lys, associated with...
Autores principales: | , , , , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
MDPI
2021
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7865823/ https://www.ncbi.nlm.nih.gov/pubmed/33499149 http://dx.doi.org/10.3390/ijms22031084 |
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author | Potrč, Maja Volk, Marija de Rosa, Matteo Pižem, Jože Teran, Nataša Jaklič, Helena Maver, Aleš Drnovšek-Olup, Brigita Bollati, Michela Vogelnik, Katarina Hočevar, Alojzija Gornik, Ana Pfeifer, Vladimir Peterlin, Borut Hawlina, Marko Fakin, Ana |
author_facet | Potrč, Maja Volk, Marija de Rosa, Matteo Pižem, Jože Teran, Nataša Jaklič, Helena Maver, Aleš Drnovšek-Olup, Brigita Bollati, Michela Vogelnik, Katarina Hočevar, Alojzija Gornik, Ana Pfeifer, Vladimir Peterlin, Borut Hawlina, Marko Fakin, Ana |
author_sort | Potrč, Maja |
collection | PubMed |
description | SIMPLE SUMMARY: Gelsolin amyloidosis is a rare autosomal dominant genetic disease, which typically affects the cornea, skin and sometimes other organ systems and is caused by mutations in a gene coding for gelsolin protein (GSN). We describe a novel mutation of GSN gene, p.Glu580Lys, associated with gelsolin amyloidosis in six members of a two-generation family, who exhibited lattice corneal dystrophy, loose facial skin and irregular heart rhythm. In one patient we reported optic nerve impairment, which is possibly a novel feature associated with gelsolin amyloidosis. 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. |
format | Online Article Text |
id | pubmed-7865823 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2021 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
spelling | pubmed-78658232021-02-07 Clinical and Histopathological Features of Gelsolin Amyloidosis Associated with a Novel GSN Variant p.Glu580Lys Potrč, Maja Volk, Marija de Rosa, Matteo Pižem, Jože Teran, Nataša Jaklič, Helena Maver, Aleš Drnovšek-Olup, Brigita Bollati, Michela Vogelnik, Katarina Hočevar, Alojzija Gornik, Ana Pfeifer, Vladimir Peterlin, Borut Hawlina, Marko Fakin, Ana Int J Mol Sci Article SIMPLE SUMMARY: Gelsolin amyloidosis is a rare autosomal dominant genetic disease, which typically affects the cornea, skin and sometimes other organ systems and is caused by mutations in a gene coding for gelsolin protein (GSN). We describe a novel mutation of GSN gene, p.Glu580Lys, associated with gelsolin amyloidosis in six members of a two-generation family, who exhibited lattice corneal dystrophy, loose facial skin and irregular heart rhythm. In one patient we reported optic nerve impairment, which is possibly a novel feature associated with gelsolin amyloidosis. 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. MDPI 2021-01-22 /pmc/articles/PMC7865823/ /pubmed/33499149 http://dx.doi.org/10.3390/ijms22031084 Text en © 2021 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/). |
spellingShingle | Article Potrč, Maja Volk, Marija de Rosa, Matteo Pižem, Jože Teran, Nataša Jaklič, Helena Maver, Aleš Drnovšek-Olup, Brigita Bollati, Michela Vogelnik, Katarina Hočevar, Alojzija Gornik, Ana Pfeifer, Vladimir Peterlin, Borut Hawlina, Marko Fakin, Ana Clinical and Histopathological Features of Gelsolin Amyloidosis Associated with a Novel GSN Variant p.Glu580Lys |
title | Clinical and Histopathological Features of Gelsolin Amyloidosis Associated with a Novel GSN Variant p.Glu580Lys |
title_full | Clinical and Histopathological Features of Gelsolin Amyloidosis Associated with a Novel GSN Variant p.Glu580Lys |
title_fullStr | Clinical and Histopathological Features of Gelsolin Amyloidosis Associated with a Novel GSN Variant p.Glu580Lys |
title_full_unstemmed | Clinical and Histopathological Features of Gelsolin Amyloidosis Associated with a Novel GSN Variant p.Glu580Lys |
title_short | Clinical and Histopathological Features of Gelsolin Amyloidosis Associated with a Novel GSN Variant p.Glu580Lys |
title_sort | clinical and histopathological features of gelsolin amyloidosis associated with a novel gsn variant p.glu580lys |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7865823/ https://www.ncbi.nlm.nih.gov/pubmed/33499149 http://dx.doi.org/10.3390/ijms22031084 |
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