{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,26]],"date-time":"2026-08-26T10:04:07Z","timestamp":1787738647376,"version":"build-2784847793"},"reference-count":15,"publisher":"Wiley","issue":"2","license":[{"start":{"date-parts":[[2017,12,12]],"date-time":"2017-12-12T00:00:00Z","timestamp":1513036800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"name":"Research Council of Oman","award":["RC\/MED\/GENT\/14\/01"],"award-info":[{"award-number":["RC\/MED\/GENT\/14\/01"]}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Euro J of Neurology"],"published-print":{"date-parts":[[2018,2]]},"abstract":"<jats:sec><jats:title>Background and purpose<\/jats:title><jats:p>Distal hereditary motor neuropathy (dHMN) due to sigma non\u2010opioid intracellular receptor 1 (<jats:italic>SIGMAR1<\/jats:italic>) gene mutation (OMIM 601978.0003) is a rare neuromuscular disorder characterized by prominent amyotrophic distal limb weakness and co\u2010existing pyramidal signs initially described in a Chinese family recently. We report an extended consanguineous Omani family segregating dHMN with pyramidal signs in an autosomal recessive pattern and describe a novel mutation in the <jats:italic>SIGMAR1<\/jats:italic> gene underlying this motor phenotype. We also provide an update on the reported phenotypic profile of <jats:italic>SIGMAR1<\/jats:italic> mutations.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>We utilized homozygosity mapping and whole\u2010exome sequencing of leucocyte DNA obtained from three affected members of an Omani family who manifested with a length\u2010dependent motor neuropathy and pyramidal signs.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>We identified a novel C&gt;T transition at nucleotide position 238 (c.238C&gt;T) in exon 2 of the <jats:italic>SIGMAR1<\/jats:italic> gene. Sanger sequencing and segregation analysis confirmed the presence of two copies of the variant in the affected subjects, unlike the unaffected healthy parents\/sibling who carried, at most, a single copy. The T allele is predicted to cause a truncating mutation (p.Gln80*), probably flagging the mRNA for nonsense\u2010mediated decay leading to a complete loss of function, thereby potentially contributing to the disease process.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>Our finding expands the spectrum of <jats:italic>SIGMAR1<\/jats:italic> mutations causing recessive dHMN and indicates that this disorder is pan\u2010ethnic. <jats:italic>SIGMAR1<\/jats:italic> mutation should be included in the diagnostic panel of a dHMN, especially if there are co\u2010existing pyramidal signs and autosomal recessive inheritance.<\/jats:p><\/jats:sec>","DOI":"10.1111\/ene.13519","type":"journal-article","created":{"date-parts":[[2017,11,8]],"date-time":"2017-11-08T12:42:43Z","timestamp":1510144963000},"page":"395-403","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":17,"title":["Recessive distal motor neuropathy with pyramidal signs in an Omani kindred: underlying novel mutation in the <i>SIGMAR1<\/i> gene"],"prefix":"10.1111","volume":"25","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-2379-0055","authenticated-orcid":false,"given":"R.","family":"Nandhagopal","sequence":"first","affiliation":[{"name":"Department of Medicine \u2013 Neurology Unit Sultan Qaboos University Hospital Muscat Oman"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"D.","family":"Meftah","sequence":"additional","affiliation":[{"name":"Genetic and Developmental Medicine Clinic Sultan Qaboos University Hospital Muscat Oman"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"S.","family":"Al\u2010Kalbani","sequence":"additional","affiliation":[{"name":"Molecular Genetics and Genomics Laboratory Sultan Qaboos University Hospital Muscat Oman"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"P.","family":"Scott","sequence":"additional","affiliation":[{"name":"Molecular Genetics and Genomics Laboratory Sultan Qaboos University Hospital Muscat Oman"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2017,12,12]]},"reference":[{"key":"e_1_2_7_2_1","doi-asserted-by":"publisher","DOI":"10.1212\/WNL.0000000000001680"},{"key":"e_1_2_7_3_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuroscience.2010.02.022"},{"key":"e_1_2_7_4_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2007.08.036"},{"key":"e_1_2_7_5_1","doi-asserted-by":"publisher","DOI":"10.1093\/brain\/awv008"},{"key":"e_1_2_7_6_1","doi-asserted-by":"publisher","DOI":"10.1038\/nbt.1754"},{"key":"e_1_2_7_7_1","doi-asserted-by":"publisher","DOI":"10.1177\/2329048X16669912"},{"key":"e_1_2_7_8_1","doi-asserted-by":"publisher","DOI":"10.1093\/hmg\/ddw220"},{"key":"e_1_2_7_9_1","doi-asserted-by":"publisher","DOI":"10.1002\/1531-8249(200012)48:6<877::AID-ANA8>3.0.CO;2-#"},{"key":"e_1_2_7_10_1","doi-asserted-by":"publisher","DOI":"10.1212\/WNL.0000000000003212"},{"key":"e_1_2_7_11_1","doi-asserted-by":"publisher","DOI":"10.1002\/ana.22534"},{"key":"e_1_2_7_12_1","doi-asserted-by":"publisher","DOI":"10.15252\/emmm.201606403"},{"key":"e_1_2_7_13_1","doi-asserted-by":"publisher","DOI":"10.1007\/s10048-015-0453-1"},{"key":"e_1_2_7_14_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neurobiolaging.2014.03.001"},{"key":"e_1_2_7_15_1","doi-asserted-by":"publisher","DOI":"10.1093\/brain\/awv173"},{"key":"e_1_2_7_16_1","doi-asserted-by":"publisher","DOI":"10.1038\/gim.2015.30"}],"container-title":["European Journal of Neurology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1111%2Fene.13519","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/ene.13519","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1111\/ene.13519","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/ene.13519","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,8,30]],"date-time":"2023-08-30T00:50:41Z","timestamp":1693356641000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1111\/ene.13519"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2017,12,12]]},"references-count":15,"journal-issue":{"issue":"2","published-print":{"date-parts":[[2018,2]]}},"alternative-id":["10.1111\/ene.13519"],"URL":"https:\/\/doi.org\/10.1111\/ene.13519","archive":["Portico"],"relation":{},"ISSN":["1351-5101","1468-1331"],"issn-type":[{"value":"1351-5101","type":"print"},{"value":"1468-1331","type":"electronic"}],"subject":[],"published":{"date-parts":[[2017,12,12]]},"assertion":[{"value":"2017-06-25","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2017-11-02","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2017-12-12","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}