{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,2]],"date-time":"2026-02-02T08:55:23Z","timestamp":1770022523371,"version":"3.49.0"},"reference-count":25,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2023,7,20]],"date-time":"2023-07-20T00:00:00Z","timestamp":1689811200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Genet."],"abstract":"<jats:p><jats:bold>Background:<\/jats:bold><jats:italic>MFN2<\/jats:italic> 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 <jats:italic>MFN2<\/jats:italic> mutation associated with ALS-frontotemporal dementia (FTD) clinical phenotype in the mother and Charcot-Marie-Tooth disease type 2A (CMT2A) in her son.<\/jats:p><jats:p><jats:bold>Case presentation:<\/jats:bold> 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\u2019 DNA identified the novel <jats:italic>MFN2<\/jats:italic> (NM_014874.4) variant c.581A&amp;gt;C p.(Asp194Ala).<\/jats:p><jats:p><jats:bold>Conclusion:<\/jats:bold> Our findings provide evidence of heterogenous clinical manifestations in family members sharing the same <jats:italic>MFN2<\/jats:italic> molecular defect. Additionally, we present the first documented case of ASL-FTD associated with an <jats:italic>MFN2<\/jats:italic> 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 <jats:italic>MFN2<\/jats:italic> as a contributing gene in the development of ALS-FTD.<\/jats:p>","DOI":"10.3389\/fgene.2023.1235887","type":"journal-article","created":{"date-parts":[[2023,7,21]],"date-time":"2023-07-21T07:52:16Z","timestamp":1689925936000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":7,"title":["Case report: Asp194Ala variant in MFN2 is associated with ALS-FTD in an Italian family"],"prefix":"10.3389","volume":"14","author":[{"given":"C.","family":"Vinciguerra","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"A.","family":"Di Fonzo","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"E.","family":"Monfrini","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"D.","family":"Ronchi","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"S.","family":"Cuoco","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"G.","family":"Piscosquito","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"P.","family":"Barone","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"M. 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