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Clinical and Histopathological Features of Gelsolin Amyloidosis Associated with a Novel GSN Variant p.Glu580Lys
- Source :
- International Journal of Molecular Sciences, Volume 22, Issue 3, International Journal of Molecular Sciences, Vol 22, Iss 1084, p 1084 (2021), International journal of molecular sciences, 22 (2021): 1–15. doi:10.3390/ijms22031084, info:cnr-pdr/source/autori:Potrc M.; Volk M.; de Rosa M.; Pizem J.; Teran N.; Jaklic H.; Maver A.; Drnovsek-Olup B.; Bollati M.; Vogelnik K.; Hocevar A.; Gornik A.; Pfeifer V.; Peterlin B.; Hawlina M.; Fakin A./titolo:Clinical and histopathological features of gelsolin amyloidosis associated with a novel gsn variant p.Glu580lys/doi:10.3390%2Fijms22031084/rivista:International journal of molecular sciences (Print)/anno:2021/pagina_da:1/pagina_a:15/intervallo_pagine:1–15/volume:22, International journal of molecular sciences, vol. 22, no. 3, 1084, 2021.
- Publication Year :
- 2021
- Publisher :
- MDPI AG, 2021.
-
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.
- Subjects :
- 0301 basic medicine
Proband
Pathology
medicine.medical_specialty
gelsolin
gelsolin amyloidosis
heart arrhythmia
cutis laxa
Corneal dystrophy
Meretoja syndrome
Catalysis
udc:617.7
lcsh:Chemistry
Inorganic Chemistry
lattice corneal dystrophy
03 medical and health sciences
symbols.namesake
0302 clinical medicine
medicine
Physical and Theoretical Chemistry
GSN
lcsh:QH301-705.5
Molecular Biology
Spectroscopy
Exome sequencing
amyloidosis
Sanger sequencing
optical coherence tomography
business.industry
Amyloidosis
Organic Chemistry
Dystrophy
General Medicine
medicine.disease
optic neuropathy
Computer Science Applications
030104 developmental biology
lcsh:Biology (General)
lcsh:QD1-999
030221 ophthalmology & optometry
symbols
Lattice corneal dystrophy
gsn
business
Gelsolin
Subjects
Details
- ISSN :
- 14220067
- Volume :
- 22
- Database :
- OpenAIRE
- Journal :
- International Journal of Molecular Sciences
- Accession number :
- edsair.doi.dedup.....20bf0c7e808fee9bc7bb3f03502cbd97
- Full Text :
- https://doi.org/10.3390/ijms22031084