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Currently, only 15% to 32.5% of patients with dHMN are characterized genetically. Additionally, the prevalence of these genetic disorders is not well known. Recently, biallelic mutations in the sorbitol dehydrogenase gene (\n                      <jats:italic>SORD<\/jats:italic>\n                      ) have been identified as a cause of dHMN, with an estimated frequency in undiagnosed cases of up to 10%.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      In the present study, we included 163 patients belonging to 108 different families who were diagnosed with a dHMN and who underwent a thorough genetic screening that included next\u2010generation sequencing and subsequent Sanger sequencing of\n                      <jats:italic>SORD<\/jats:italic>\n                      .\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      Most probands were sporadic cases (62.3%), and the most frequent age of onset of symptoms was 2 to 10\u00a0years (28.8%). A genetic diagnosis was achieved in 37\/108 (34.2%) families and 78\/163 (47.8%) of all patients. The most frequent cause of distal hereditary motor neuropathies were mutations in\n                      <jats:italic>HSPB1<\/jats:italic>\n                      (10.4%),\n                      <jats:italic>GARS1<\/jats:italic>\n                      (9.8%),\n                      <jats:italic>BICD2<\/jats:italic>\n                      (8.0%), and\n                      <jats:italic>DNAJB2<\/jats:italic>\n                      (6.7%) genes. In addition, 3.1% of patients were found to be carriers of biallelic mutations in\n                      <jats:italic>SORD<\/jats:italic>\n                      . Mutations in another seven genes were also identified, although they were much less frequent. Eight new pathogenic mutations were detected, and 17 patients without a definite genetic diagnosis carried variants of uncertain significance. The calculated minimum prevalence of dHMN was 2.3 per 100,000 individuals.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>\n                      This study confirms the genetic heterogeneity of dHMN and that biallelic\n                      <jats:italic>SORD<\/jats:italic>\n                      mutations are a cause of dHMN in different populations.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1111\/ene.14700","type":"journal-article","created":{"date-parts":[[2020,12,28]],"date-time":"2020-12-28T16:17:46Z","timestamp":1609172266000},"page":"1334-1343","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":71,"title":["Distal hereditary motor neuropathies: Mutation spectrum and genotype\u2013phenotype 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