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Biallelic variants in\n                      <jats:italic toggle=\"yes\">SIGMAR1<\/jats:italic>\n                      , encoding sigma nonopioid intracellular receptor 1, have been linked to autosomal recessive dHMN with pyramidal features. This study investigated the clinical and genetic features of patients with dHMN associated with\n                      <jats:italic toggle=\"yes\">SIGMAR1<\/jats:italic>\n                      variants in Japan.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      We conducted genetic screening of Japanese patients with clinically suspected inherited peripheral neuropathies using targeted gene panels and whole-exome sequencing.\n                      <jats:italic toggle=\"yes\">SIGMAR1<\/jats:italic>\n                      variants were evaluated via segregation analysis using Sanger sequencing. Detailed clinical and electrophysiological data were systematically reviewed.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      Biallelic\n                      <jats:italic toggle=\"yes\">SIGMAR1<\/jats:italic>\n                      variants, including three novel variants and one previously reported variant, were identified in six patients from five unrelated families. The genotypes comprised compound heterozygous variants in four patients and homozygous variants in two patients. All patients presented with early-onset distal muscle weakness and atrophy. Enhanced tendon reflexes and pyramidal tract signs were frequently observed, whereas bulbar or respiratory involvement was absent. Nerve conduction studies consistently revealed motor-predominant axonal neuropathy with minimal sensory involvement. Disease progression was slow, and all patients remained ambulatory for years to decades after onset.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>\n                      Our findings expand the clinical and genetic spectrum of\n                      <jats:italic toggle=\"yes\">SIGMAR1<\/jats:italic>\n                      -associated disease and support its classification as dHMN rather than ALS.\n                      <jats:italic toggle=\"yes\">SIGMAR1<\/jats:italic>\n                      variants should be considered in the genetic evaluation of early-onset motor neuropathies, particularly in patients with dHMN accompanied by pyramidal features.\n                    <\/jats:p>\n                  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