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


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.

SUBMITTER: Potrc M 

PROVIDER: S-EPMC7865823 | biostudies-literature | 2021 Jan

REPOSITORIES: biostudies-literature

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

Potrč Maja M   Volk Marija M   de Rosa Matteo M   Pižem Jože J   Teran Nataša N   Jaklič Helena H   Maver Aleš A   Drnovšek-Olup Brigita B   Bollati Michela M   Vogelnik Katarina K   Hočevar Alojzija A   Gornik Ana A   Pfeifer Vladimir V   Peterlin Borut B   Hawlina Marko M   Fakin Ana A  

International journal of molecular sciences 20210122 3


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  ...[more]

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