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Case report: Asp194Ala variant in MFN2 is associated with ALS-FTD in an Italian family

Background: MFN2 gene encodes the protein Mitofusin 2, involved in essential mitochondrial functions such as fusion, trafficking, turnover, and cellular interactions. We describe a family carrying a novel MFN2 mutation associated with ALS-frontotemporal dementia (FTD) clinical phenotype in the mothe...

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Autores principales: Vinciguerra, C., Di Fonzo, A., Monfrini, E., Ronchi, D., Cuoco, S., Piscosquito, G., Barone, P., Pellecchia, M. T
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10400291/
https://www.ncbi.nlm.nih.gov/pubmed/37547466
http://dx.doi.org/10.3389/fgene.2023.1235887
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author Vinciguerra, C.
Di Fonzo, A.
Monfrini, E.
Ronchi, D.
Cuoco, S.
Piscosquito, G.
Barone, P.
Pellecchia, M. T
author_facet Vinciguerra, C.
Di Fonzo, A.
Monfrini, E.
Ronchi, D.
Cuoco, S.
Piscosquito, G.
Barone, P.
Pellecchia, M. T
author_sort Vinciguerra, C.
collection PubMed
description Background: MFN2 gene encodes the protein Mitofusin 2, involved in essential mitochondrial functions such as fusion, trafficking, turnover, and cellular interactions. We describe a family carrying a novel MFN2 mutation associated with ALS-frontotemporal dementia (FTD) clinical phenotype in the mother and Charcot-Marie-Tooth disease type 2A (CMT2A) in her son. Case presentation: The mother, a 67-year-old woman, referred to us for a three year-history of mood disturbance and gait impairment, and a more recent hypophonia, dysarthria, dysphagia, and diffuse muscle wasting. Family history was positive for psychiatric disorders and gait disturbances. Brain 18F-FDG PET showed severe hypometabolism in the fronto-temporal brain cortex bilaterally. Electrodiagnostic studies (EDX) showed severe motor axonopathy in the bulbar, cervical and lumbosacral districts. Her 41-year-old son had a history of mood depression and sensory disturbances in the limbs, along with mild muscle wasting, weakness, and reduced reflexes. Nerve conduction studies revealed a moderate sensory-motor polyneuropathy, while brain MRI was normal. Whole exome sequencing of the patients’ DNA identified the novel MFN2 (NM_014874.4) variant c.581A>C p.(Asp194Ala). Conclusion: Our findings provide evidence of heterogenous clinical manifestations in family members sharing the same MFN2 molecular defect. Additionally, we present the first documented case of ASL-FTD associated with an MFN2 mutation, thereby expanding the range of MFN-related disorders. Further research involving larger cohorts of patients will be needed to better understand the role of MFN2 as a contributing gene in the development of ALS-FTD.
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spelling pubmed-104002912023-08-04 Case report: Asp194Ala variant in MFN2 is associated with ALS-FTD in an Italian family Vinciguerra, C. Di Fonzo, A. Monfrini, E. Ronchi, D. Cuoco, S. Piscosquito, G. Barone, P. Pellecchia, M. T Front Genet Genetics Background: MFN2 gene encodes the protein Mitofusin 2, involved in essential mitochondrial functions such as fusion, trafficking, turnover, and cellular interactions. We describe a family carrying a novel MFN2 mutation associated with ALS-frontotemporal dementia (FTD) clinical phenotype in the mother and Charcot-Marie-Tooth disease type 2A (CMT2A) in her son. Case presentation: The mother, a 67-year-old woman, referred to us for a three year-history of mood disturbance and gait impairment, and a more recent hypophonia, dysarthria, dysphagia, and diffuse muscle wasting. Family history was positive for psychiatric disorders and gait disturbances. Brain 18F-FDG PET showed severe hypometabolism in the fronto-temporal brain cortex bilaterally. Electrodiagnostic studies (EDX) showed severe motor axonopathy in the bulbar, cervical and lumbosacral districts. Her 41-year-old son had a history of mood depression and sensory disturbances in the limbs, along with mild muscle wasting, weakness, and reduced reflexes. Nerve conduction studies revealed a moderate sensory-motor polyneuropathy, while brain MRI was normal. Whole exome sequencing of the patients’ DNA identified the novel MFN2 (NM_014874.4) variant c.581A>C p.(Asp194Ala). Conclusion: Our findings provide evidence of heterogenous clinical manifestations in family members sharing the same MFN2 molecular defect. Additionally, we present the first documented case of ASL-FTD associated with an MFN2 mutation, thereby expanding the range of MFN-related disorders. Further research involving larger cohorts of patients will be needed to better understand the role of MFN2 as a contributing gene in the development of ALS-FTD. Frontiers Media S.A. 2023-07-20 /pmc/articles/PMC10400291/ /pubmed/37547466 http://dx.doi.org/10.3389/fgene.2023.1235887 Text en Copyright © 2023 Vinciguerra, Di Fonzo, Monfrini, Ronchi, Cuoco, Piscosquito, Barone and Pellecchia. https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Genetics
Vinciguerra, C.
Di Fonzo, A.
Monfrini, E.
Ronchi, D.
Cuoco, S.
Piscosquito, G.
Barone, P.
Pellecchia, M. T
Case report: Asp194Ala variant in MFN2 is associated with ALS-FTD in an Italian family
title Case report: Asp194Ala variant in MFN2 is associated with ALS-FTD in an Italian family
title_full Case report: Asp194Ala variant in MFN2 is associated with ALS-FTD in an Italian family
title_fullStr Case report: Asp194Ala variant in MFN2 is associated with ALS-FTD in an Italian family
title_full_unstemmed Case report: Asp194Ala variant in MFN2 is associated with ALS-FTD in an Italian family
title_short Case report: Asp194Ala variant in MFN2 is associated with ALS-FTD in an Italian family
title_sort case report: asp194ala variant in mfn2 is associated with als-ftd in an italian family
topic Genetics
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10400291/
https://www.ncbi.nlm.nih.gov/pubmed/37547466
http://dx.doi.org/10.3389/fgene.2023.1235887
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