{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,11,13]],"date-time":"2025-11-13T02:06:14Z","timestamp":1762999574074,"version":"3.41.2"},"reference-count":36,"publisher":"Wiley","issue":"8","license":[{"start":{"date-parts":[[2020,4,16]],"date-time":"2020-04-16T00:00:00Z","timestamp":1586995200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/501100002403","name":"Taibah University","doi-asserted-by":"publisher","award":["Deanship of Scientific Research\u201010057"],"award-info":[{"award-number":["Deanship of Scientific Research\u201010057"]}],"id":[{"id":"10.13039\/501100002403","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["The Journal of Gene Medicine"],"published-print":{"date-parts":[[2020,8]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Background<\/jats:title><jats:p>Progressive spastic ataxia is a heterogeneous disorder characterized by cerebellar ataxia and limb spasticity associated with other severe neurological complications. Spastic ataxia is classified into pure and complex types, inherited in both an autosomal recessive and autosomal dominant manner. It is caused by pathogenic variants in at least eight different genes, including <jats:italic>NKX6\u20102<\/jats:italic> (MIM 607063) located on chromosome 10q26.3. The present study aimed to identify the genetic variant(s) underlying progressive spastic ataxia and to establish the genotype\u2013phenotype correlation.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>We collected a large consanguineous family having four affected individuals segregating progressive spastic ataxia in an autosomal recessive manner. To investigate the molecular cause of the disease, genomic DNA of three affected individuals underwent whole exome sequencing.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>All of the affected individuals showed progressive clinical features such as spastic ataxia, lower limb weakness and other mild neurological abnormalities. Whole exome sequencing data were analyzed using different filters. Filtering of rare and shared homozygous variants revealed a novel homozygous missense variant (c.545C&gt;T; p.Ala182Val) in a highly conserved homeobox domain of the NKX6\u20102 protein.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>The findings of the present study add a novel variant to the <jats:italic>NKX6\u20102<\/jats:italic> mutation spectrum and provide evidence that homozygous variants in the <jats:italic>NKX6\u20102<\/jats:italic> cause progressive spastic ataxia associated with other abnormalities.<\/jats:p><\/jats:sec>","DOI":"10.1002\/jgm.3196","type":"journal-article","created":{"date-parts":[[2020,4,4]],"date-time":"2020-04-04T20:18:46Z","timestamp":1586031526000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":5,"title":["A homozygous missense variant in the homeobox domain of the <i>NKX6\u20102<\/i> results in progressive spastic ataxia type 8 associated with lower limb weakness and neurological manifestations"],"prefix":"10.1002","volume":"22","author":[{"given":"Ahmad","family":"Almatrafi","sequence":"first","affiliation":[{"name":"Department of Biology, College of Science Taibah University  Almadinah Almunawwarah Saudi Arabia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Muhammad","family":"Umair","sequence":"additional","affiliation":[{"name":"Medical Genomics Research Department, King Abdullah International Medical Research Center (KAIMRC) King Saud Bin Abdulaziz University for Health Sciences, Ministry of National Guard\u2010Health Affairs (MNGHA)  Riyadh Saudi Arabia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Amr","family":"Eldardear","sequence":"additional","affiliation":[{"name":"College of Medicine Taibah University  Almadinah Almunawwarah Saudi Arabia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Majid","family":"Al\u2010Luqmani","sequence":"additional","affiliation":[{"name":"College of Medicine Taibah University  Almadinah Almunawwarah Saudi Arabia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jamil A.","family":"Hashmi","sequence":"additional","affiliation":[{"name":"Center for Genetics and Inherited Diseases Taibah University  Medina Saudi Arabia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Alia M.","family":"Albalawi","sequence":"additional","affiliation":[{"name":"Center for Genetics and Inherited Diseases Taibah University  Medina Saudi Arabia"},{"name":"Department of Biology, College of Science King Abdulaziz University Jeddah  Jeddah Saudi Arabia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Majid","family":"Alfadhel","sequence":"additional","affiliation":[{"name":"Medical Genomics Research Department, King Abdullah International Medical Research Center (KAIMRC) King Saud Bin Abdulaziz University for Health Sciences, Ministry of National Guard\u2010Health Affairs (MNGHA)  Riyadh Saudi Arabia"},{"name":"Division of Genetics, Department of Pediatrics King Abdullah Specialized Children's Hospital (KASCH), King Abdulaziz Medical City  Riyadh Saudi Arabia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Khushnooda","family":"Ramzan","sequence":"additional","affiliation":[{"name":"Department of Genetics King Faisal Specialist Hospital and Research Centre  Riyadh Saudi Arabia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4294-6825","authenticated-orcid":false,"given":"Sulman","family":"Basit","sequence":"additional","affiliation":[{"name":"Center for Genetics and Inherited Diseases Taibah University  Medina Saudi Arabia"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2020,4,16]]},"reference":[{"key":"e_1_2_9_2_1","first-page":"1208","article-title":"Ataxia","volume":"22","author":"Ashizawa T","year":"2016","journal-title":"Continuum (Minneap Minn)"},{"key":"e_1_2_9_3_1","doi-asserted-by":"publisher","DOI":"10.1086\/338933"},{"key":"e_1_2_9_4_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ajhg.2012.07.018"},{"key":"e_1_2_9_5_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pgen.1002325"},{"key":"e_1_2_9_6_1","doi-asserted-by":"publisher","DOI":"10.1007\/s12311-013-0538-z"},{"key":"e_1_2_9_7_1","doi-asserted-by":"publisher","DOI":"10.1007\/s12311-019-01036-2"},{"key":"e_1_2_9_8_1","doi-asserted-by":"publisher","DOI":"10.1136\/jmedgenet-2013-102012"},{"key":"e_1_2_9_9_1","first-page":"9","article-title":"KIF1C variants are associated with Hypomyelination, ataxia, tremor, and dystonia in fraternal twins","volume":"17","author":"Marchionni E","year":"2019","journal-title":"Tremor Other Hyperkinet Mov (N Y)"},{"key":"e_1_2_9_10_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pbio.1001288"},{"key":"e_1_2_9_11_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ajhg.2010.09.013"},{"key":"e_1_2_9_12_1","doi-asserted-by":"publisher","DOI":"10.1038\/ejhg.2008.58"},{"key":"e_1_2_9_13_1","doi-asserted-by":"publisher","DOI":"10.1007\/s12031-009-9212-9"},{"key":"e_1_2_9_14_1","doi-asserted-by":"publisher","DOI":"10.1212\/WNL.0b013e3181f4d86c"},{"key":"e_1_2_9_15_1","doi-asserted-by":"publisher","DOI":"10.1007\/s12311-013-0451-5"},{"key":"e_1_2_9_16_1","doi-asserted-by":"publisher","DOI":"10.1007\/s12311-019-01028-2"},{"key":"e_1_2_9_17_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ajhg.2017.05.009"},{"key":"e_1_2_9_18_1","doi-asserted-by":"publisher","DOI":"10.1111\/ene.14082"},{"key":"e_1_2_9_19_1","doi-asserted-by":"publisher","DOI":"10.1093\/brain\/awx207"},{"key":"e_1_2_9_20_1","doi-asserted-by":"publisher","DOI":"10.1111\/cge.13221"},{"key":"e_1_2_9_21_1","doi-asserted-by":"publisher","DOI":"10.1212\/NXG.0000000000000209"},{"key":"e_1_2_9_22_1","first-page":"1993","volume-title":"GeneReviews\u00ae","author":"Chelban V","year":"2018"},{"key":"e_1_2_9_23_1","doi-asserted-by":"publisher","DOI":"10.1002\/mgg3.627"},{"key":"e_1_2_9_24_1","doi-asserted-by":"publisher","DOI":"10.1111\/cge.13152"},{"key":"e_1_2_9_25_1","doi-asserted-by":"publisher","DOI":"10.1038\/jhg.2015.129"},{"key":"e_1_2_9_26_1","doi-asserted-by":"publisher","DOI":"10.1038\/pr.2017.149"},{"key":"e_1_2_9_27_1","first-page":"90","article-title":"Whole exome sequencing as a diagnostic tool for genetic disorders in Pakistan","volume":"57","author":"Umair M","year":"2018","journal-title":"Pak J Med Res"},{"key":"e_1_2_9_28_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00439-017-1843-2"},{"key":"e_1_2_9_29_1","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.17-17-06657.1997"},{"key":"e_1_2_9_30_1","doi-asserted-by":"publisher","DOI":"10.1002\/1097-4547(20000815)61:4<376::AID-JNR4>3.0.CO;2-#"},{"key":"e_1_2_9_31_1","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.3479-04.2004"},{"key":"e_1_2_9_32_1","doi-asserted-by":"publisher","DOI":"10.1002\/glia.20937"},{"key":"e_1_2_9_33_1","doi-asserted-by":"publisher","DOI":"10.1016\/0092-8674(90)90453-L"},{"key":"e_1_2_9_34_1","doi-asserted-by":"publisher","DOI":"10.1016\/0092-8674(94)90292-5"},{"key":"e_1_2_9_35_1","doi-asserted-by":"publisher","DOI":"10.1007\/BF01668504"},{"key":"e_1_2_9_36_1","doi-asserted-by":"publisher","DOI":"10.1023\/A:1006908013972"},{"key":"e_1_2_9_37_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.devcel.2010.05.015"}],"container-title":["The Journal of Gene Medicine"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1002%2Fjgm.3196","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/jgm.3196","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1002\/jgm.3196","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/jgm.3196","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,9,5]],"date-time":"2023-09-05T09:16:44Z","timestamp":1693905404000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1002\/jgm.3196"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2020,4,16]]},"references-count":36,"journal-issue":{"issue":"8","published-print":{"date-parts":[[2020,8]]}},"alternative-id":["10.1002\/jgm.3196"],"URL":"https:\/\/doi.org\/10.1002\/jgm.3196","archive":["Portico"],"relation":{},"ISSN":["1099-498X","1521-2254"],"issn-type":[{"type":"print","value":"1099-498X"},{"type":"electronic","value":"1521-2254"}],"subject":[],"published":{"date-parts":[[2020,4,16]]},"assertion":[{"value":"2020-02-16","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2020-03-25","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2020-04-16","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"e3196"}}