Clinical and histopathological features of gelsolin amyloidosis associated with a novel GSN variant p.Glu580Lys

Potrč, Maja (author), Volk, Marija (author), de Rosa, Matteo (author), Pižem, Jože (author), Teran, Nataša (author), Jaklič, Helena (author), Maver, Aleš (author), Drnovšek-Olup, Brigita (author), Bollati, Michela (author), Vogelnik, Katarina (author), Hočevar, Alojzija (author), Gornik, Ana (author), Pfeifer, Vladimir (author), Peterlin, Borut (author), Hawlina, Marko (author), Fakin, Ana (author)

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.

• Language: English
• Keywords: gelsolin amyloidosis, Meretoja syndrome, GSN, cutis laxa, heart arrhythmia, lattice corneal dystrophy, optic neuropathy, optical coherence tomography
• Work type: Article
• Typology: 1.01 - Original Scientific Article
• Organization: MF - Faculty of Medicine
• Publication status: Published
• Publication version: Version of Record
• Year: 2021
• Number of pages: 15 str.
• Numbering: Vol. 22, iss. 3, art. 1084
• PID: 20.500.12556/RUL-134888
• UDC: 617.7
• ISSN on article: 1422-0067
• DOI: 10.3390/ijms22031084
• COBISS.SI-ID: 49715203
• Publication date in RUL: 10.02.2022

Record is a part of a journal

• Title: International journal of molecular sciences
• Shortened title: Int. j. mol. sci.
• Publisher: MDPI
• ISSN: 1422-0067
• COBISS.SI-ID: 2779162

Licences

• License: CC BY 4.0, Creative Commons Attribution 4.0 International
• Link: http://creativecommons.org/licenses/by/4.0/
• Description: This is the standard Creative Commons license that gives others maximum freedom to do what they want with the work as long as they credit the author.
• Licensing start date: 01.02.2021

Projects

• Funder: ARRS - Slovenian Research Agency
• Project number: J3-1750
• Name: Priprava pogojev za gensko zdravljenje dednih očesnih bolezni