{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,11,28]],"date-time":"2025-11-28T12:35:53Z","timestamp":1764333353145,"version":"3.40.5"},"reference-count":24,"publisher":"Wiley","issue":"4","license":[{"start":{"date-parts":[[2023,11,6]],"date-time":"2023-11-06T00:00:00Z","timestamp":1699228800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/501100008353","name":"Funda\u00e7\u00e3o de Apoio ao Ensino, Pesquisa e Assist\u00eancia do Hospital das Cl\u00ednicas da Faculdade de Medicina de Ribeir\u00e3o Preto da Universidade de S\u00e3o Paulo","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100008353","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["J Peripheral Nervous Sys"],"published-print":{"date-parts":[[2023,12]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Background and Aims<\/jats:title><jats:p>X\u2010linked Charcot\u2013Marie\u2013Tooth disease type 6 (CMTX6) is an extremely rare condition associated with mutations in the PDK3 gene. To date, only three families from different countries have been reported (Australia, South Korea, and Germany). In this study, we sought to provide a comprehensive clinical and electrophysiological characterization of two Brazilian families.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>We conducted comprehensive clinical assessments, extensive electrophysiological evaluations, and performed whole\u2010exome sequencing in the probands to investigate the genetic basis of the disease.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Males in the family carrying the Arg162His mutation displayed early\u2010onset motor and\/or sensory axonal neuropathy, absence of tendon jerks, <jats:italic>pes cavus<\/jats:italic>, and frequently reported pain. Females in the same family exhibited a milder phenotype of the disease with later onset and some remained asymptomatic into their 50s. In the unrelated family with a single affected male, the clinical presentation was characterized by severe progressive sensorimotor polyneuropathy accompanied by neuropathic pain.<\/jats:p><\/jats:sec><jats:sec><jats:title>Interpretation<\/jats:title><jats:p>We report two Brazilian families with CMTX6 including one harboring a previously unpublished variant in the PDK3 gene, which co\u2010segregates with the disease as expected in a X\u2010linked disease. Notably, the clinical presentations across the five families with available descriptions, including our study, share striking similarities. Furthermore, the proximity of the three reported mutations suggests potential functional similarities and common underlying mechanisms. This study contributes to the growing knowledge of CMTX6 and underscores the importance of international collaborations in studying rare genetic disorders.<\/jats:p><\/jats:sec>","DOI":"10.1111\/jns.12601","type":"journal-article","created":{"date-parts":[[2023,10,18]],"date-time":"2023-10-18T04:51:50Z","timestamp":1697604710000},"page":"614-619","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Unveiling the clinical and electrophysiological profile of <scp>CMTX6<\/scp>: Insights from two Brazilian families"],"prefix":"10.1111","volume":"28","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-6425-3646","authenticated-orcid":false,"given":"Victor Augusto Zanesi","family":"Maciel","sequence":"first","affiliation":[{"name":"Department of Neurosciences and Behavior Sciences Hospital das Cl\u00ednicas da Faculdade de Medicina de Ribeir\u00e3o Preto \u2013 USP (HCRP\u2010USP)  Ribeir\u00e3o Preto Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Gustavo","family":"Maximiano\u2010Alves","sequence":"additional","affiliation":[{"name":"Department of Neurosciences and Behavior Sciences Hospital das Cl\u00ednicas da Faculdade de Medicina de Ribeir\u00e3o Preto \u2013 USP (HCRP\u2010USP)  Ribeir\u00e3o Preto Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4325-3414","authenticated-orcid":false,"given":"Rodrigo Siqueira Soares","family":"Frezatti","sequence":"additional","affiliation":[{"name":"Department of Neurosciences and Behavior Sciences Hospital das Cl\u00ednicas da Faculdade de Medicina de Ribeir\u00e3o Preto \u2013 USP (HCRP\u2010USP)  Ribeir\u00e3o Preto Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Anna Let\u00edcia De Moraes","family":"Alves","sequence":"additional","affiliation":[{"name":"Department of Neurosciences and Behavior Sciences Hospital das Cl\u00ednicas da Faculdade de Medicina de Ribeir\u00e3o Preto \u2013 USP (HCRP\u2010USP)  Ribeir\u00e3o Preto Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Bianca Mara Alves","family":"Andrade","sequence":"additional","affiliation":[{"name":"Department of Neurosciences and Behavior Sciences Hospital das Cl\u00ednicas da Faculdade de Medicina de Ribeir\u00e3o Preto \u2013 USP (HCRP\u2010USP)  Ribeir\u00e3o Preto Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Rita De Cassia Carvalho","family":"Leal","sequence":"additional","affiliation":[{"name":"Department of Neurosciences and Behavior Sciences Hospital das Cl\u00ednicas da Faculdade de Medicina de Ribeir\u00e3o Preto \u2013 USP (HCRP\u2010USP)  Ribeir\u00e3o Preto Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1485-3771","authenticated-orcid":false,"given":"Pedro 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