{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,28]],"date-time":"2026-03-28T08:42:49Z","timestamp":1774687369669,"version":"3.50.1"},"reference-count":6,"publisher":"Wiley","issue":"8","license":[{"start":{"date-parts":[[2023,5,16]],"date-time":"2023-05-16T00:00:00Z","timestamp":1684195200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["American J of Med Genetics Pt A"],"published-print":{"date-parts":[[2023,8]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Alzahrani\u2013Kuwahara syndrome (ALKUS) is a neurodevelopmental disorder that includes microcephaly, facial dysmorphism, and variable congenital and eye malformations. We present the first case of ALKUS described in the European population caused by two variants in compound heterozygosity of the gene <jats:italic>SMG8.<\/jats:italic> We present a patient with two variants in compound heterozygosity in the <jats:italic>SMG8<\/jats:italic> gene identified by in trio whole exome sequencing based in next generation sequencing (xGEN\u00ae Exome Research Panel, Nextseq550 platform). International case reporting (CARE) criteria were followed. Patient written consent was obtained through legal responsible persons. We describe a 27\u2010year\u2010old male, the second child of a healthy and non\u2010consanguineous couple, whose genetic analysis showed two variants in compound heterozygosity, c.1159C\u2009&gt;\u2009T (p.Arg387*) and c.2407del (p.Arg803Glyfs*10), in the <jats:italic>SMG8<\/jats:italic> gene, both classified as likely pathogenic. As described by Fatema Alzahrani et al. in a series of eight patients, our patient had global developmental delay with impaired intellectual development, facial dysmorphism, and limb disproportion. Additionally, our patient had lower limb spastic paraparesis, marked osteotendinous hyperreflexia with extensor plantar response bilaterally and paretic gait. Our patient resembles the phenotype described by Fatema Alzahrani et al., however, he is the first patient with two <jats:italic>SMG8<\/jats:italic> deleterious variants in compound heterozygosity, and the first to exhibit pyramidal signs and gait disorder as part of the phenotype.<\/jats:p>","DOI":"10.1002\/ajmg.a.63242","type":"journal-article","created":{"date-parts":[[2023,5,17]],"date-time":"2023-05-17T03:54:42Z","timestamp":1684295682000},"page":"2204-2208","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Expanding the genetic spectrum of <scp>ALKU<\/scp> syndrome: Compound heterozygosity for two deleterious variants in <scp><i>SMG8<\/i><\/scp> gene"],"prefix":"10.1002","volume":"191","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-2975-9323","authenticated-orcid":false,"given":"Andr\u00e9 Aires","family":"Fernandes","sequence":"first","affiliation":[{"name":"Servi\u00e7o de Neurologia Centro Hospitalar Universit\u00e1rio de S\u00e3o Jo\u00e3o  Porto Portugal"},{"name":"Departamento de Neuroci\u00eancias Cl\u00ednicas e Sa\u00fade Mental Faculdade de Medicina da Universidade do Porto  Porto Portugal"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3183-9154","authenticated-orcid":false,"given":"Ana","family":"Grangeia","sequence":"additional","affiliation":[{"name":"Servi\u00e7o de Gen\u00e9tica M\u00e9dica Centro Hospitalar Universit\u00e1rio de S\u00e3o Jo\u00e3o  Porto Portugal"},{"name":"Servi\u00e7o de Gen\u00e9tica Faculdade de Medicina da Universidade do Porto  Porto Portugal"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Leonor","family":"Dias","sequence":"additional","affiliation":[{"name":"Servi\u00e7o de Neurologia Centro Hospitalar Universit\u00e1rio de S\u00e3o Jo\u00e3o  Porto Portugal"},{"name":"Departamento de Neuroci\u00eancias Cl\u00ednicas e Sa\u00fade Mental Faculdade de Medicina da Universidade do Porto  Porto Portugal"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Joana","family":"Guimar\u00e3es","sequence":"additional","affiliation":[{"name":"Servi\u00e7o de Neurologia Centro Hospitalar Universit\u00e1rio de S\u00e3o Jo\u00e3o  Porto Portugal"},{"name":"Departamento de Neuroci\u00eancias Cl\u00ednicas e Sa\u00fade Mental Faculdade de Medicina da Universidade do Porto  Porto Portugal"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2023,5,16]]},"reference":[{"key":"e_1_2_8_2_1","doi-asserted-by":"publisher","DOI":"10.1002\/ajmg.a.62561"},{"key":"e_1_2_8_3_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ajhg.2020.11.007"},{"key":"e_1_2_8_4_1","volume-title":"Handbook of physical measurements","author":"Hall J.","year":"2006"},{"key":"e_1_2_8_5_1","doi-asserted-by":"publisher","DOI":"10.1038\/gim.2015.30"},{"key":"e_1_2_8_6_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ajhg.2016.02.010"},{"key":"e_1_2_8_7_1","doi-asserted-by":"publisher","DOI":"10.1038\/ng2100"}],"container-title":["American Journal of Medical Genetics Part A"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/ajmg.a.63242","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,8,23]],"date-time":"2023-08-23T12:23:54Z","timestamp":1692793434000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1002\/ajmg.a.63242"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,5,16]]},"references-count":6,"journal-issue":{"issue":"8","published-print":{"date-parts":[[2023,8]]}},"alternative-id":["10.1002\/ajmg.a.63242"],"URL":"https:\/\/doi.org\/10.1002\/ajmg.a.63242","archive":["Portico"],"relation":{},"ISSN":["1552-4825","1552-4833"],"issn-type":[{"value":"1552-4825","type":"print"},{"value":"1552-4833","type":"electronic"}],"subject":[],"published":{"date-parts":[[2023,5,16]]},"assertion":[{"value":"2022-12-08","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2023-05-03","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2023-05-16","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}