A new heterozygous G duplicate in exon1 (c.100dupG) of gelsolin gene causes Finnish gelsolin amyloidosis in a Chinese family

Abstract

ObjectivesIn this study, we report a case of Finnish gelsolin amyloidosis (FGA) in a Chinese family.MethodsThe proband presented with a range of clinical symptoms that included epileptic seizures and multiple lesions in the brain. Whole exome sequencing of the Gelsolin (GSN) gene was performed, and the GSN mutation was identified through comparison with the known human genome sequences using Genetic Testing Intelligent Execution System.ResultsThe GSN gene sequencing revealed that a heterozygous G duplicate in exon1 (c.100dupG) of the GSN gene, which caused a frameshift in GSN transcript translation in the proband, his mother and daughter, but his brother did not have it.ConclusionWe presented a new autosomal dominant heterozygous G duplicate mutation in exon1 of GSN gene, leading to FGA in a Chinese family.

Analyses Mutations in GSN, CST3, TTR, and ITM2B Genes in Chinese Patients With Alzheimer’s Disease

“…Followed by G194R and N211K mutations, whose clinical phenotype is different from D214N/Y, mainly gelsolin-related renal amyloidosis (Sethi et al, 2013;Efebera et al, 2014). A34fs, P459R, and A578P mutations were reported recently, corresponding totally different manifestations from mutations that we mentioned before (Feng et al, 2018;Oregel et al, 2018;Sridharan et al, 2018; Table 4). Patients with A34fs mutation presented with seizures and brain lesions, without skin and eye symptoms.…”

“…Due to the frame shift at the start site, some scholars believed that it might not translate the functional domain of gelsolin. Therefore, the amyloid protein formed by the A34fs mutation might have different composition relative to other FAF fibrils China (Feng et al, 2018) Atypical FAF Not known, maybe brain and cerebral vessels.…”

“…The GSN gene is located on the chromosome 9q33.2 and is inherited by dominance. Up to now, seven pathogenic mutations in the GSN gene have been reported in worldwide, namely A34fs, G194R, N211K, D214N, D214Y, P459R, and A578P ( Figure 2 and Table 4 , Hiltunen et al, 1991 ; Stewart et al, 2000 ; Conceição et al, 2003 ; Chastan et al, 2006 ; Ardalan et al, 2007 ; Huerva et al, 2007 ; Carrwik and Stenevi, 2009 ; Luttmann et al, 2010 ; Makioka et al, 2010 ; Asahina et al, 2011 ; Solari et al, 2011 ; Taira et al, 2012 ; Sethi et al, 2013 ; Efebera et al, 2014 ; Park et al, 2016 ; Caress et al, 2017 ; de Souza et al, 2017 ; Feng et al, 2018 ; Mustonen et al, 2018 ; Oregel et al, 2018 ; Sridharan et al, 2018 ). The D214N/Y mutation is the most common mutation and could cause the disease of FAF, which mainly manifested as corneal lattice dystrophy, cranial neuropathy, peripheral neuropathy, and cutis laxa (Nikoskinen et al, 2015 ).…”

“…FAF has also been reported in other areas besides Finland. Due to differences in regions and races, it could be seen that, in East Asia, the clinical manifestations of FAF were mainly neurological symptoms (Taira et al, 2012 ; Park et al, 2016 ; Feng et al, 2018 ). Followed by G194R and N211K mutations, whose clinical phenotype is different from D214N/Y, mainly gelsolin-related renal amyloidosis (Sethi et al, 2013 ; Efebera et al, 2014 ).…”

“…*Novel mutation. (Feng et al, 2018;Zorgati et al, 2019). Both patients with A34fs and P3fs mutations mainly presented with central nervous symptoms, without skin, eyes, and peripheral nervous symptoms.…”