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

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

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.

• Jezik: Angleški jezik
• Ključne besede: gelsolin amyloidosis, Meretoja syndrome, GSN, cutis laxa, heart arrhythmia, lattice corneal dystrophy, optic neuropathy, optical coherence tomography
• Vrsta gradiva: Članek v reviji
• Tipologija: 1.01 - Izvirni znanstveni članek
• Organizacija: MF - Medicinska fakulteta
• Status publikacije: Objavljeno
• Različica publikacije: Objavljena publikacija
• Leto izida: 2021
• Št. strani: 15 str.
• Številčenje: Vol. 22, iss. 3, art. 1084
• PID: 20.500.12556/RUL-134888
• UDK: 617.7
• ISSN pri članku: 1422-0067
• DOI: 10.3390/ijms22031084
• COBISS.SI-ID: 49715203
• Datum objave v RUL: 10.02.2022

Gradivo je del revije

• Naslov: International journal of molecular sciences
• Skrajšan naslov: Int. j. mol. sci.
• Založnik: MDPI
• ISSN: 1422-0067
• COBISS.SI-ID: 2779162

Licence

• Licenca: CC BY 4.0, Creative Commons Priznanje avtorstva 4.0 Mednarodna
• Povezava: http://creativecommons.org/licenses/by/4.0/deed.sl
• Opis: To je standardna licenca Creative Commons, ki daje uporabnikom največ možnosti za nadaljnjo uporabo dela, pri čemer morajo navesti avtorja.
• Začetek licenciranja: 01.02.2021

Projekti

• Financer: ARRS - Agencija za raziskovalno dejavnost Republike Slovenije
• Številka projekta: J3-1750
• Naslov: Priprava pogojev za gensko zdravljenje dednih očesnih bolezni