{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,1,26]],"date-time":"2026-01-26T19:28:25Z","timestamp":1769455705362,"version":"3.49.0"},"reference-count":55,"publisher":"Wiley","issue":"6","license":[{"start":{"date-parts":[[2023,3,3]],"date-time":"2023-03-03T00:00:00Z","timestamp":1677801600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100012155","name":"National Institute for Medical Research Development","doi-asserted-by":"publisher","award":["971846"],"award-info":[{"award-number":["971846"]}],"id":[{"id":"10.13039\/501100012155","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Molec Gen &amp;amp; Gen Med"],"published-print":{"date-parts":[[2023,6]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Background<\/jats:title><jats:p>Giant axonal neuropathy (GAN) is a progressive childhood hereditary polyneuropathy that affects both the peripheral and central nervous systems. Disease\u2010causing variants in the gigaxonin gene (<jats:italic>GAN<\/jats:italic>) cause autosomal recessive giant axonal neuropathy. Facial weakness, nystagmus, scoliosis, kinky or curly hair, pyramidal and cerebellar signs, and sensory and motor axonal neuropathy are the main symptoms of this disorder. Here, we report two novel variants in the <jats:italic>GAN<\/jats:italic> gene from two unrelated Iranian families.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Clinical and imaging data of patients were recorded and evaluated, retrospectively. Whole\u2010exome sequencing (WES) was undertaken in order to detect disease\u2010causing variants in participants. Confirmation of a causative variant in all three patients and their parents was carried out using Sanger sequencing and segregation analysis. In addition, for comparing to our cases, we reviewed all relevant clinical data of previously published cases of GAN between the years 2013\u20132020.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Three patients from two unrelated families were included. Using WES, we identified a novel nonsense variant [NM_022041.3:c.1162del (p.Leu388Ter)], in a 7\u2010year\u2010old boy of family 1, and a likely pathogenic missense variant [NM_022041.3:c.370T&gt;A (p.Phe124Ile)], in two affected siblings of the family 2. Clinical examination revealed typical features of GAN\u20101 in all three patients, including walking difficulties, ataxic gait, kinky hair, sensory\u2010motor polyneuropathy, and nonspecific neuroimaging abnormalities. Review of 63 previously reported cases of GAN indicated unique kinky hair, gait problem, hyporeflexia\/areflexia, and sensory impairment were the most commonly reported clinical features.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>One homozygous nonsense variant and one homozygous missense variant in the <jats:italic>GAN<\/jats:italic> gene were discovered for the first time in two unrelated Iranian families that expand the mutation spectrum of GAN. Imaging findings are nonspecific, but the electrophysiological study in addition to history is helpful to achieve the diagnosis. The molecular test confirms the diagnosis.<\/jats:p><\/jats:sec>","DOI":"10.1002\/mgg3.2159","type":"journal-article","created":{"date-parts":[[2023,3,3]],"date-time":"2023-03-03T08:22:38Z","timestamp":1677831758000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":8,"title":["Expanding the genetic spectrum of giant axonal neuropathy: Two novel variants in Iranian families"],"prefix":"10.1002","volume":"11","author":[{"given":"Mahmoud Reza","family":"Ashrafi","sequence":"first","affiliation":[{"name":"Ataxia Clinic, Pediatric Neurology Division, Children's Medical Center, Pediatrics Center of Excellence Tehran University of Medical Sciences  Tehran Iran"},{"name":"Department of Paediatrics, Division of Paediatric Neurology, Growth and Development Research Center, Children's Medical Centre, Paediatrics Centre of Excellence Tehran University of Medical Sciences  Tehran Iran"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ali Zare","family":"Dehnavi","sequence":"additional","affiliation":[{"name":"Ataxia Clinic, Pediatric Neurology Division, Children's Medical Center, Pediatrics Center of Excellence Tehran University of Medical Sciences  Tehran Iran"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ali Reza","family":"Tavasoli","sequence":"additional","affiliation":[{"name":"Ataxia Clinic, Pediatric Neurology Division, Children's Medical Center, Pediatrics Center of Excellence Tehran University of Medical Sciences  Tehran Iran"},{"name":"Myelin Disorders Clinic, Pediatric Neurology Division, Children's Medical Center, Pediatrics Center of Excellence Tehran University of Medical Sciences  Tehran Iran"},{"name":"Jefferson Institute of Molecular Medicine Thomas Jefferson University  Philadelphia Pennsylvania USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Morteza","family":"Heidari","sequence":"additional","affiliation":[{"name":"Ataxia Clinic, Pediatric Neurology Division, Children's Medical Center, Pediatrics Center of Excellence Tehran University of Medical Sciences  Tehran Iran"},{"name":"Myelin Disorders Clinic, Pediatric Neurology Division, Children's Medical Center, Pediatrics Center of Excellence Tehran University of Medical Sciences  Tehran Iran"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Masoud","family":"Ghahvechi\u00a0Akbari","sequence":"additional","affiliation":[{"name":"Ataxia Clinic, Pediatric Neurology Division, Children's Medical Center, Pediatrics Center of Excellence Tehran University of Medical Sciences  Tehran Iran"},{"name":"Physical Medicine and Rehabilitation department, Children's Medical Center Tehran University of Medical Sciences  Tehran Iran"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ali Reza","family":"Ronagh","sequence":"additional","affiliation":[{"name":"Pediatric Neurology Department Alborz University of Medical Sciences  Karaj Iran"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mohammad","family":"Ghafouri","sequence":"additional","affiliation":[{"name":"Ataxia Clinic, Pediatric Neurology Division, Children's Medical Center, Pediatrics Center of Excellence Tehran University of Medical Sciences  Tehran Iran"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Nejat","family":"Mahdieh","sequence":"additional","affiliation":[{"name":"Genetic Research Center, Rajaei Cardiovascular Medical and Research Center Iran University of Medical Sciences  Tehran Iran"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Pouria","family":"Mohammadi","sequence":"additional","affiliation":[{"name":"Ataxia Clinic, Pediatric Neurology Division, Children's Medical Center, Pediatrics Center of Excellence Tehran University of Medical Sciences  Tehran Iran"},{"name":"Department of Medical Genetics, Faculty of Medical Sciences Tarbiat Modares University  Tehran Iran"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4966-6658","authenticated-orcid":false,"given":"Zahra","family":"Rezaei","sequence":"additional","affiliation":[{"name":"Ataxia Clinic, Pediatric Neurology Division, Children's Medical Center, Pediatrics Center of Excellence Tehran University of Medical Sciences  Tehran Iran"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2023,3,3]]},"reference":[{"key":"e_1_2_11_2_1","doi-asserted-by":"publisher","DOI":"10.1093\/bioinformatics\/btv506"},{"key":"e_1_2_11_3_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ejpn.2012.10.012"},{"key":"e_1_2_11_4_1","doi-asserted-by":"publisher","DOI":"10.1186\/s12881-016-0343-x"},{"key":"e_1_2_11_5_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.braindev.2011.02.003"},{"key":"e_1_2_11_6_1","doi-asserted-by":"publisher","DOI":"10.1038\/nature04256"},{"key":"e_1_2_11_7_1","doi-asserted-by":"publisher","DOI":"10.1590\/abd1806-4841.20164677"},{"key":"e_1_2_11_8_1","doi-asserted-by":"publisher","DOI":"10.1186\/s13023-018-0957-5"},{"key":"e_1_2_11_9_1","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/gkw408"},{"key":"e_1_2_11_10_1","doi-asserted-by":"publisher","DOI":"10.1136\/bmjopen-2018-021632"},{"key":"e_1_2_11_11_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.omtm.2018.02.005"},{"key":"e_1_2_11_12_1","doi-asserted-by":"publisher","DOI":"10.1038\/81701"},{"key":"e_1_2_11_13_1","doi-asserted-by":"publisher","DOI":"10.1002\/ajmg.a.33508"},{"key":"e_1_2_11_14_1","doi-asserted-by":"publisher","DOI":"10.4103\/0366-6999.241804"},{"key":"e_1_2_11_15_1","volume-title":"Exome_pipe: An automatic exome data analysis pipeline","author":"Choi Y.","year":"2016"},{"issue":"1","key":"e_1_2_11_16_1","first-page":"82","article-title":"Pymol: An open\u2010source molecular graphics tool","volume":"40","author":"DeLano W. L.","year":"2002","journal-title":"Protein Crystallography"},{"key":"e_1_2_11_17_1","doi-asserted-by":"publisher","DOI":"10.1083\/jcb.200202055"},{"key":"e_1_2_11_18_1","doi-asserted-by":"publisher","DOI":"10.1007\/s10048-019-00596-z"},{"key":"e_1_2_11_19_1","doi-asserted-by":"publisher","DOI":"10.24953\/turkjped.2019.02.019"},{"key":"e_1_2_11_20_1","doi-asserted-by":"publisher","DOI":"10.4103\/0972-2327.91960"},{"key":"e_1_2_11_21_1","doi-asserted-by":"publisher","DOI":"10.1007\/978-94-024-1045-7_10"},{"key":"e_1_2_11_22_1","doi-asserted-by":"publisher","DOI":"10.1002\/ajmg.a.62592"},{"key":"e_1_2_11_23_1","doi-asserted-by":"publisher","DOI":"10.1016\/B978-0-444-52902-2.00052-7"},{"key":"e_1_2_11_24_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.arcped.2018.09.006"},{"key":"e_1_2_11_25_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.braindev.2014.12.002"},{"key":"e_1_2_11_26_1","doi-asserted-by":"publisher","DOI":"10.1093\/hmg\/ddw081"},{"key":"e_1_2_11_27_1","doi-asserted-by":"publisher","DOI":"10.1212\/WNL.0000000000000177"},{"key":"e_1_2_11_28_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1529-8027.2012.00409.x"},{"key":"e_1_2_11_29_1","doi-asserted-by":"publisher","DOI":"10.1017\/cjn.2014.102"},{"key":"e_1_2_11_30_1","doi-asserted-by":"publisher","DOI":"10.1002\/mus.24321"},{"key":"e_1_2_11_31_1","doi-asserted-by":"publisher","DOI":"10.1080\/10826068.2017.1303613"},{"key":"e_1_2_11_32_1","doi-asserted-by":"publisher","DOI":"10.1136\/bcr-2014-204481"},{"key":"e_1_2_11_33_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00439-016-1659-5"},{"key":"e_1_2_11_34_1","doi-asserted-by":"publisher","DOI":"10.1212\/WNL.0000000000000206"},{"key":"e_1_2_11_35_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.braindev.2015.09.001"},{"key":"e_1_2_11_36_1","doi-asserted-by":"publisher","DOI":"10.1091\/mbc.E15-09-0627"},{"key":"e_1_2_11_37_1","doi-asserted-by":"publisher","DOI":"10.1186\/s13059-016-0974-4"},{"key":"e_1_2_11_38_1","doi-asserted-by":"publisher","DOI":"10.1111\/cge.12455"},{"key":"e_1_2_11_39_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jocn.2013.06.017"},{"key":"e_1_2_11_40_1","doi-asserted-by":"publisher","DOI":"10.1007\/s13760-020-01527-8"},{"key":"e_1_2_11_41_1","first-page":"1","article-title":"A novel homozygous missense variant in the NAXE gene in an Iranian family with progressive encephalopathy with brain edema and leukoencephalopathy","volume":"122","author":"Mohammadi P.","year":"2021","journal-title":"Acta Neurologica Belgica"},{"key":"e_1_2_11_42_1","doi-asserted-by":"publisher","DOI":"10.1002\/mgg3.1834"},{"key":"e_1_2_11_43_1","doi-asserted-by":"publisher","DOI":"10.1089\/hum.2012.107"},{"key":"e_1_2_11_44_1","doi-asserted-by":"publisher","DOI":"10.1007\/s12519-018-0140-z"},{"key":"e_1_2_11_45_1","doi-asserted-by":"publisher","DOI":"10.1177\/1176934318760543"},{"key":"e_1_2_11_46_1","doi-asserted-by":"publisher","DOI":"10.1038\/gim.2015.30"},{"key":"e_1_2_11_47_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.nmd.2013.06.007"},{"key":"e_1_2_11_48_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cca.2019.12.017"},{"key":"e_1_2_11_49_1","doi-asserted-by":"publisher","DOI":"10.1097\/MD.0000000000001749"},{"key":"e_1_2_11_50_1","doi-asserted-by":"publisher","DOI":"10.1177\/0883073814547721"},{"key":"e_1_2_11_51_1","doi-asserted-by":"publisher","DOI":"10.1002\/mus.24130"},{"key":"e_1_2_11_52_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cub.2005.10.052"},{"key":"e_1_2_11_53_1","doi-asserted-by":"publisher","DOI":"10.3109\/01658107.2013.814149"},{"key":"e_1_2_11_54_1","doi-asserted-by":"publisher","DOI":"10.3389\/fnins.2020.00085"},{"key":"e_1_2_11_55_1","doi-asserted-by":"publisher","DOI":"10.1101\/cshperspect.a018309"},{"key":"e_1_2_11_56_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M501279200"}],"container-title":["Molecular Genetics &amp; Genomic Medicine"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/mgg3.2159","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1002\/mgg3.2159","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/mgg3.2159","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,8,20]],"date-time":"2023-08-20T16:09:22Z","timestamp":1692547762000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1002\/mgg3.2159"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,3,3]]},"references-count":55,"journal-issue":{"issue":"6","published-print":{"date-parts":[[2023,6]]}},"alternative-id":["10.1002\/mgg3.2159"],"URL":"https:\/\/doi.org\/10.1002\/mgg3.2159","archive":["Portico"],"relation":{},"ISSN":["2324-9269","2324-9269"],"issn-type":[{"value":"2324-9269","type":"print"},{"value":"2324-9269","type":"electronic"}],"subject":[],"published":{"date-parts":[[2023,3,3]]},"assertion":[{"value":"2021-11-15","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2023-02-09","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2023-03-03","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"e2159"}}