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MTMR5\/SBF1 is a pseudophosphatase predicted to regulate endo-lysosomal trafficking in tandem with other MTMRs. Although almost ubiquitously expressed, pathogenic variants primarily impact on the peripheral nervous system, corroborating the involvement of MTMR5\/SBF1 and its molecular partners in Schwann cells-mediated myelinization.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Case presentation<\/jats:title>\n                    <jats:p>\n                      We report a case of severe CMT4B3 characterized by early-onset motor and axonal polyneuropathy in an Italian child in absence of any evidence of brain and spine MRI abnormalities or intellectual disability and with a biochemical profile suggestive of mitochondrial disease. Using an integrated approach combining both NGS gene panels and WES analysis, we identified two novel compound heterozygous missense variants in MTMR5\/\n                      <jats:italic>SBF1<\/jats:italic>\n                      gene, p.R763H (c.2291G\u2009&gt;\u2009A) and p.G1064E (c.3194G\u2009&gt;\u2009A). Studies in muscle identified partial defects of oxidative metabolism.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>\n                      We describe the first case of an early onset severe polyneuropathy with motor and axonal involvement, due to recessive variants in the MTMR5\/\n                      <jats:italic>SBF1<\/jats:italic>\n                      gene, with no evidence of brain and spine MRI abnormalities, intellectual disability, no clinical and neurophysiological evidences of distal sensory impairment, and rapid neuromuscular deterioration. This report suggests that MTMR5\/\n                      <jats:italic>SBF1<\/jats:italic>\n                      should be considered in cases of infantile-onset CMT with secondary mitochondrial dysfunction.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1186\/s12920-021-01001-1","type":"journal-article","created":{"date-parts":[[2021,6,12]],"date-time":"2021-06-12T13:02:43Z","timestamp":1623502963000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":12,"title":["Bi-allelic variants in MTMR5\/SBF1 cause Charcot-Marie-Tooth type 4B3 featuring mitochondrial dysfunction"],"prefix":"10.1186","volume":"14","author":[{"given":"Beatrice","family":"Berti","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Giovanna","family":"Longo","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Francesco","family":"Mari","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stefano","family":"Doccini","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ilaria","family":"Piccolo","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maria Alice","family":"Donati","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Francesca","family":"Moro","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Renzo","family":"Guerrini","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1359-9062","authenticated-orcid":false,"given":"Filippo M.","family":"Santorelli","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8771-6033","authenticated-orcid":false,"given":"Vittoria","family":"Petruzzella","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2021,6,12]]},"reference":[{"issue":"4","key":"1001_CR1","doi-asserted-by":"publisher","first-page":"667","DOI":"10.1016\/j.bbadis.2014.07.031","volume":"1852","author":"NU Jerath","year":"2015","unstructured":"Jerath NU, Shy ME. 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