Clinical and Histopathological Features of Gelsolin Amyloidosis Associated with a Novel <i>GSN</i> Variant p.Glu580Lys
Gelsolin amyloidosis typically presents with corneal lattice dystrophy and is most frequently associated with pathogenic <i>GSN</i> variant p.Asp214Asn. Here we report clinical and histopathological features of gelsolin amyloidosis associated with a novel <i>GSN</i> variant p...
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doaj-d8d75b2f377c427099932851715d11702021-01-23T00:02:27ZengMDPI AGInternational Journal of Molecular Sciences1661-65961422-00672021-01-01221084108410.3390/ijms22031084Clinical and Histopathological Features of Gelsolin Amyloidosis Associated with a Novel <i>GSN</i> Variant p.Glu580LysMaja Potrč0Marija Volk1Matteo de Rosa2Jože Pižem3Nataša Teran4Helena Jaklič5Aleš Maver6Brigita Drnovšek-Olup7Michela Bollati8Katarina Vogelnik9Alojzija Hočevar10Ana Gornik11Vladimir Pfeifer12Borut Peterlin13Marko Hawlina14Ana Fakin15Eye Hospital, University Medical Centre Ljubljana, 1000 Ljubljana, SloveniaClinical Institute of Genomic Medicine, University Medical Centre Ljubljana, 1000 Ljubljana, SloveniaInstitute of Biophysics, National Research Council, 20133 Milano, ItalyInstitute of Pathology, Faculty of Medicine, University of Ljubljana, 1000 Ljubljana, SloveniaClinical Institute of Genomic Medicine, University Medical Centre Ljubljana, 1000 Ljubljana, SloveniaClinical Institute of Genomic Medicine, University Medical Centre Ljubljana, 1000 Ljubljana, SloveniaClinical Institute of Genomic Medicine, University Medical Centre Ljubljana, 1000 Ljubljana, SloveniaEye Hospital, University Medical Centre Ljubljana, 1000 Ljubljana, SloveniaInstitute of Biophysics, National Research Council, 20133 Milano, ItalyDepartment of Neurology, University of Ljubljana, 1000 Ljubljana, SloveniaDepartment of Rheumatology, University Medical Centre Ljubljana, 1000 Ljubljana, SloveniaEye Hospital, University Medical Centre Ljubljana, 1000 Ljubljana, SloveniaEye Hospital, University Medical Centre Ljubljana, 1000 Ljubljana, SloveniaClinical Institute of Genomic Medicine, University Medical Centre Ljubljana, 1000 Ljubljana, SloveniaEye Hospital, University Medical Centre Ljubljana, 1000 Ljubljana, SloveniaEye Hospital, University Medical Centre Ljubljana, 1000 Ljubljana, SloveniaGelsolin amyloidosis typically presents with corneal lattice dystrophy and is most frequently associated with pathogenic <i>GSN</i> variant p.Asp214Asn. Here we report clinical and histopathological features of gelsolin amyloidosis associated with a novel <i>GSN</i> 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 <i>GSN</i> 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.https://www.mdpi.com/1422-0067/22/3/1084gelsolin amyloidosisMeretoja syndromelattice corneal dystrophyoptic neuropathy<i>GSN</i>cutis laxa |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Maja Potrč Marija Volk Matteo de Rosa Jože Pižem Nataša Teran Helena Jaklič Aleš Maver Brigita Drnovšek-Olup Michela Bollati Katarina Vogelnik Alojzija Hočevar Ana Gornik Vladimir Pfeifer Borut Peterlin Marko Hawlina Ana Fakin |
spellingShingle |
Maja Potrč Marija Volk Matteo de Rosa Jože Pižem Nataša Teran Helena Jaklič Aleš Maver Brigita Drnovšek-Olup Michela Bollati Katarina Vogelnik Alojzija Hočevar Ana Gornik Vladimir Pfeifer Borut Peterlin Marko Hawlina Ana Fakin Clinical and Histopathological Features of Gelsolin Amyloidosis Associated with a Novel <i>GSN</i> Variant p.Glu580Lys International Journal of Molecular Sciences gelsolin amyloidosis Meretoja syndrome lattice corneal dystrophy optic neuropathy <i>GSN</i> cutis laxa |
author_facet |
Maja Potrč Marija Volk Matteo de Rosa Jože Pižem Nataša Teran Helena Jaklič Aleš Maver Brigita Drnovšek-Olup Michela Bollati Katarina Vogelnik Alojzija Hočevar Ana Gornik Vladimir Pfeifer Borut Peterlin Marko Hawlina Ana Fakin |
author_sort |
Maja Potrč |
title |
Clinical and Histopathological Features of Gelsolin Amyloidosis Associated with a Novel <i>GSN</i> Variant p.Glu580Lys |
title_short |
Clinical and Histopathological Features of Gelsolin Amyloidosis Associated with a Novel <i>GSN</i> Variant p.Glu580Lys |
title_full |
Clinical and Histopathological Features of Gelsolin Amyloidosis Associated with a Novel <i>GSN</i> Variant p.Glu580Lys |
title_fullStr |
Clinical and Histopathological Features of Gelsolin Amyloidosis Associated with a Novel <i>GSN</i> Variant p.Glu580Lys |
title_full_unstemmed |
Clinical and Histopathological Features of Gelsolin Amyloidosis Associated with a Novel <i>GSN</i> Variant p.Glu580Lys |
title_sort |
clinical and histopathological features of gelsolin amyloidosis associated with a novel <i>gsn</i> variant p.glu580lys |
publisher |
MDPI AG |
series |
International Journal of Molecular Sciences |
issn |
1661-6596 1422-0067 |
publishDate |
2021-01-01 |
description |
Gelsolin amyloidosis typically presents with corneal lattice dystrophy and is most frequently associated with pathogenic <i>GSN</i> variant p.Asp214Asn. Here we report clinical and histopathological features of gelsolin amyloidosis associated with a novel <i>GSN</i> 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 <i>GSN</i> 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. |
topic |
gelsolin amyloidosis Meretoja syndrome lattice corneal dystrophy optic neuropathy <i>GSN</i> cutis laxa |
url |
https://www.mdpi.com/1422-0067/22/3/1084 |
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