{"doi":"10.1002/mus.70314","title":"Two Patients With Juvenile‐Onset, Rapidly Progressive Amyotrophic Lateral Sclerosis Associated With an\n                    <scp>SOD1</scp>\n                    Variant (\n                    <scp>p.Asp125Gly</scp>\n                    ) With Incomplete Penetrance","abstract":"<jats:title>ABSTRACT</jats:title>\n                  <jats:sec>\n                    <jats:title>Introduction/Aims</jats:title>\n                    <jats:p>\n                      Amyotrophic lateral sclerosis (ALS) patients are rarely encountered before age 25 years, often associated with genetic variants.\n                      <jats:italic>SOD1</jats:italic>\n                      gene variants are well‐known to account for a subset of adult‐onset ALS but have only been described in a handful of early onset patients. Variants affecting residue 125 in\n                      <jats:italic>SOD1</jats:italic>\n                      have been described in adult‐onset ALS patients with a rapid progression. Here we report two such patients.\n                    </jats:p>\n                  </jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods</jats:title>\n                    <jats:p>\n                      The clinical, genetic, and electrodiagnostic findings of two unrelated adolescents with juvenile onset rapidly progressive\n                      <jats:styled-content style=\"fixed-case\">\n                        <jats:italic>SOD1</jats:italic>\n                      </jats:styled-content>\n                      ‐\n                      <jats:styled-content style=\"fixed-case\">ALS</jats:styled-content>\n                      are described.\n                    </jats:p>\n                  </jats:sec>\n                  <jats:sec>\n                    <jats:title>Results</jats:title>\n                    <jats:p>\n                      Patient 1 presented at 16 and patient 2 at 15 years‐of‐age with lower limb onset of weakness, lower motor neuron examination findings, and rapid progression over months to involve all body regions. Both patients underwent extensive laboratory, electrophysiologic, and radiologic testing ruling out any alternate etiologies. For both patients, whole‐exome sequencing revealed the pathogenic variant p.\n                      <jats:styled-content style=\"fixed-case\">Asp125Gly</jats:styled-content>\n                      in the\n                      <jats:styled-content style=\"fixed-case\">\n                        <jats:italic>SOD1</jats:italic>\n                      </jats:styled-content>\n                      gene inherited from asymptomatic fathers.\n                    </jats:p>\n                  </jats:sec>\n                  <jats:sec>\n                    <jats:title>Discussion</jats:title>\n                    <jats:p>\n                      These two patients expand the phenotypic spectrum of\n                      <jats:styled-content style=\"fixed-case\">\n                        <jats:italic>SOD1</jats:italic>\n                      </jats:styled-content>\n                      ‐\n                      <jats:styled-content style=\"fixed-case\">ALS</jats:styled-content>\n                      , demonstrating a rapidly progressive juvenile lower limb onset phenotype associated with the p.\n                      <jats:styled-content style=\"fixed-case\">Asp125Gly</jats:styled-content>\n                      variant inherited with incomplete penetrance. Recognition and further characterization of juvenile\n                      <jats:styled-content style=\"fixed-case\">\n                        <jats:italic>SOD1</jats:italic>\n                      </jats:styled-content>\n                      ‐\n                      <jats:styled-content style=\"fixed-case\">ALS</jats:styled-content>\n                      are important in light of the advances in targeted therapies.\n                    </jats:p>\n                  </jats:sec>","journal":"Muscle &amp; Nerve","year":2026,"id":652306,"datarank":0.0,"base_score":0.0,"endowment":0.0,"self_citation_contribution":0.0,"citation_network_contribution":0.0,"self_endowment_contribution":0.0,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":0,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":null,"is_data_producer":false,"deposit_databanks":null,"is_oa":false,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":null,"fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":1701554,"name":"Abigail Schwaede","orcid":"0000-0002-2574-2217","position":1,"is_corresponding":false},{"id":1701555,"name":"Bridget McGowan","orcid":null,"position":2,"is_corresponding":false},{"id":752180,"name":"Li Zhang","orcid":"0000-0001-5705-6548","position":3,"is_corresponding":false},{"id":1701556,"name":"Martha Finch","orcid":"0009-0004-3801-1554","position":4,"is_corresponding":false},{"id":555464,"name":"Lisa F. Wolfe","orcid":"0000-0001-9044-4147","position":5,"is_corresponding":false},{"id":651555,"name":"Senda Ajroud‐Driss","orcid":"0000-0001-7627-425X","position":6,"is_corresponding":false},{"id":236109,"name":"Colin K. Franz","orcid":"0000-0003-4546-8638","position":7,"is_corresponding":false},{"id":1701559,"name":"Nancy Kuntz","orcid":null,"position":8,"is_corresponding":false},{"id":1701553,"name":"Can Ozlu","orcid":"0000-0002-3643-1422","position":0,"is_corresponding":false}],"reference_count":0,"raw_metadata":{"has_enrichment":true,"resolved":true,"title":"Two Patients With Juvenile‐Onset, Rapidly Progressive Amyotrophic Lateral Sclerosis Associated With an\n                    <scp>SOD1</scp>\n                    Variant (\n                    <scp>p.Asp125Gly</scp>\n                    ) With Incomplete Penetrance","abstract":"<jats:title>ABSTRACT</jats:title>\n                  <jats:sec>\n                    <jats:title>Introduction/Aims</jats:title>\n                    <jats:p>\n                      Amyotrophic lateral sclerosis (ALS) patients are rarely encountered before age 25 years, often associated with genetic variants.\n                      <jats:italic>SOD1</jats:italic>\n                      gene variants are well‐known to account for a subset of adult‐onset ALS but have only been described in a handful of early onset patients. Variants affecting residue 125 in\n                      <jats:italic>SOD1</jats:italic>\n                      have been described in adult‐onset ALS patients with a rapid progression. Here we report two such patients.\n                    </jats:p>\n                  </jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods</jats:title>\n                    <jats:p>\n                      The clinical, genetic, and electrodiagnostic findings of two unrelated adolescents with juvenile onset rapidly progressive\n                      <jats:styled-content style=\"fixed-case\">\n                        <jats:italic>SOD1</jats:italic>\n                      </jats:styled-content>\n                      ‐\n                      <jats:styled-content style=\"fixed-case\">ALS</jats:styled-content>\n                      are described.\n                    </jats:p>\n                  </jats:sec>\n                  <jats:sec>\n                    <jats:title>Results</jats:title>\n                    <jats:p>\n                      Patient 1 presented at 16 and patient 2 at 15 years‐of‐age with lower limb onset of weakness, lower motor neuron examination findings, and rapid progression over months to involve all body regions. Both patients underwent extensive laboratory, electrophysiologic, and radiologic testing ruling out any alternate etiologies. For both patients, whole‐exome sequencing revealed the pathogenic variant p.\n                      <jats:styled-content style=\"fixed-case\">Asp125Gly</jats:styled-content>\n                      in the\n                      <jats:styled-content style=\"fixed-case\">\n                        <jats:italic>SOD1</jats:italic>\n                      </jats:styled-content>\n                      gene inherited from asymptomatic fathers.\n                    </jats:p>\n                  </jats:sec>\n                  <jats:sec>\n                    <jats:title>Discussion</jats:title>\n                    <jats:p>\n                      These two patients expand the phenotypic spectrum of\n                      <jats:styled-content style=\"fixed-case\">\n                        <jats:italic>SOD1</jats:italic>\n                      </jats:styled-content>\n                      ‐\n                      <jats:styled-content style=\"fixed-case\">ALS</jats:styled-content>\n                      , demonstrating a rapidly progressive juvenile lower limb onset phenotype associated with the p.\n                      <jats:styled-content style=\"fixed-case\">Asp125Gly</jats:styled-content>\n                      variant inherited with incomplete penetrance. Recognition and further characterization of juvenile\n                      <jats:styled-content style=\"fixed-case\">\n                        <jats:italic>SOD1</jats:italic>\n                      </jats:styled-content>\n                      ‐\n                      <jats:styled-content style=\"fixed-case\">ALS</jats:styled-content>\n                      are important in light of the advances in targeted therapies.\n                    </jats:p>\n                  </jats:sec>","is_dataset_classified":null,"base_score":0.0,"endowment":0.0,"datacite_reuse_total":0,"file_count":0,"downloads":0,"views":0,"has_version_chain":false,"is_dataset":false,"is_oa":false,"pmid":"42265995","pmcid":null,"openalex_id":"https://openalex.org/W7164160172","authors":[],"funders":[],"total_grants":0,"fwci":0.0,"citation_percentile":0.73953757,"influential_citations":0,"citation_trend":[],"oa_status":"closed","license":"http://doi.wiley.com/10.1002/tdm_license_1.1","oa_locations":[{"url":"https://onlinelibrary.wiley.com/doi/pdf/10.1002/mus.70314","host_type":"publisher"},{"url":"https://onlinelibrary.wiley.com/doi/full-xml/10.1002/mus.70314","host_type":"publisher"},{"url":"https://doi.org/10.1002/mus.70314","host_type":"journal"},{"url":"https://pubmed.ncbi.nlm.nih.gov/42265995","host_type":"repository"}],"fields_of_study":["Amyotrophic Lateral Sclerosis Research","Genetic Neurodegenerative Diseases","Hereditary Neurological Disorders","Humans","Amyotrophic Lateral Sclerosis","Superoxide Dismutase-1","Male","Adolescent","Disease Progression","Penetrance","Female","Age of Onset","Mutation"],"mesh_terms":["Superoxide Dismutase-1","Adolescent","Amyotrophic Lateral Sclerosis","Female","Humans","Male","Mutation","Age of Onset","Disease Progression","Penetrance"],"keywords":["Amyotrophic lateral sclerosis","Penetrance","SOD1","Asymptomatic","Age of onset","Progressive muscular atrophy","Genetic testing","Familial Als","Juvenile Als"],"sdg_mappings":[{"sdg_number":0,"sdg_label":"Good health and well-being"}],"linked_datasets":[],"clinical_trials":[],"software_tools":[],"database_accessions":[],"source":"live","citation_network_status":"fetched"},"created_at":"2026-08-10T12:56:49.520093Z","pmid":null,"pmcid":null,"fwci":null,"citation_percentile":null,"influential_citations":0,"oa_status":null,"license":null,"views":0,"total_file_size_bytes":0,"version_count":0,"fair_f":null,"fair_a":null,"fair_i":null,"fair_r":null,"fair_zscore":null,"fair_rationale":null,"fair_model":null,"fair_agent_version":null,"fair_fulltext_source":null,"fair_has_llm":null,"fair_computed_at":null,"clinical_trials":[],"software_tools":[],"db_accessions":[],"linked_datasets":[],"topics":[]}