{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,1,8]],"date-time":"2026-01-08T20:46:50Z","timestamp":1767905210739,"version":"3.49.0"},"reference-count":24,"publisher":"MDPI AG","issue":"12","license":[{"start":{"date-parts":[[2024,11,29]],"date-time":"2024-11-29T00:00:00Z","timestamp":1732838400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Genes"],"abstract":"<jats:p>Background\/Objectives: Axonal Charcot\u2013Marie\u2013Tooth disease type 2 (CMT2) accounts for 24% of Hereditary Motor\/Sensory Peripheral Neuropathies. CMT2 type GG, due to four distinct heterozygous mutations in the Golgi brefeldin A resistant guanine nucleotide exchange factor 1 (GBF1) gene (OMIM 606483), was described in seven cases from four unrelated families with autosomal dominant inheritance. It is characterized by slowly progressive distal muscle weakness and atrophy, primarily affecting the lower limbs. Here, we present two siblings sharing a novel GBF1 variant. Methods: Patient II.1 (male, 61 years at onset) presented lower limb hypoesthesia and walking difficulty; the examination revealed a postural tremor, a positive Romberg test, and muscle atrophy in the lower limbs and hands. Patient II.2 (his sister, 59 years at onset) had lower limb dysesthesias, hand paresthesia, and lower-limb stiffness. They underwent clinical evaluations, blood tests, and electroneurography. Their father represents a potentially affected individual, although a genetic analysis was not conducted. Results: All tests for peripheral neuropathies were unremarkable, including metabolic and autoimmune screening. Both showed a mixed demyelinating\u2013axonal sensory\u2013motor neuropathy. Genetic analysis revealed a new heterozygous GBF1 variant of uncertain significance. Conclusions: Based on autosomal dominant inheritance, as well as clinical and physiological features, a possible novel CMT2GG was diagnosed. Further research, including functional assays and in vitro studies, is necessary to confirm this variant\u2019s causal link.<\/jats:p>","DOI":"10.3390\/genes15121556","type":"journal-article","created":{"date-parts":[[2024,12,2]],"date-time":"2024-12-02T03:50:57Z","timestamp":1733111457000},"page":"1556","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["A Novel GBF1 Variant in a Charcot-Marie-Tooth Type 2: Insights from Familial Analysis"],"prefix":"10.3390","volume":"15","author":[{"given":"Valentina","family":"Ciampana","sequence":"first","affiliation":[{"name":"Neurology Unit, Department of Translational Medicine, Maggiore Della Carit\u00e0 Hospital, University of Piemonte Orientale, 28100 Novara, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1737-8267","authenticated-orcid":false,"given":"Lucia","family":"Corrado","sequence":"additional","affiliation":[{"name":"Department of Translational Medicine, Genetic Laboratory, Universit\u00e0 del Piemonte Orientale (UPO), 28100 Novara, Italy"},{"name":"Department of Health Sciences, Center on Autoimmune and Allergic Diseases (CAAD), University of Piemonte Orientale (UPO), 28100 Novara, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9546-8567","authenticated-orcid":false,"given":"Luca","family":"Magistrelli","sequence":"additional","affiliation":[{"name":"Parkinson Institute of Milan, ASST G.Pini-CTO, 20122 Milano, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0218-5251","authenticated-orcid":false,"given":"Elena","family":"Contaldi","sequence":"additional","affiliation":[{"name":"Parkinson Institute of Milan, ASST G.Pini-CTO, 20122 Milano, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6862-9468","authenticated-orcid":false,"given":"Cristoforo","family":"Comi","sequence":"additional","affiliation":[{"name":"Neurology Unit, Department of Translational Medicine, Maggiore Della Carit\u00e0 Hospital, University of Piemonte Orientale, 28100 Novara, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sandra","family":"D\u2019Alfonso","sequence":"additional","affiliation":[{"name":"Department of Health Sciences, Center on Autoimmune and Allergic Diseases (CAAD), University of Piemonte Orientale (UPO), 28100 Novara, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5920-9210","authenticated-orcid":false,"given":"Domizia","family":"Vecchio","sequence":"additional","affiliation":[{"name":"Neurology Unit, Department of Translational Medicine, Maggiore Della Carit\u00e0 Hospital, University of Piemonte Orientale, 28100 Novara, Italy"},{"name":"Department of Health Sciences, Center on Autoimmune and Allergic Diseases (CAAD), University of Piemonte Orientale (UPO), 28100 Novara, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2024,11,29]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"259","DOI":"10.1093\/brain\/103.2.259","article-title":"The clinical features of hereditary motor and sensory neuropathy types I and II","volume":"103","author":"Harding","year":"1980","journal-title":"Brain"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"2461","DOI":"10.1111\/ene.15860","article-title":"Clinical spectrum and frequency of Charcot-Marie-Tooth disease in Italy: Data from the National CMT Registry","volume":"30","author":"Pisciotta","year":"2023","journal-title":"Eur. 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