{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,23]],"date-time":"2026-08-23T14:58:53Z","timestamp":1787497133820,"version":"build-2736575974"},"reference-count":18,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2022,3,23]],"date-time":"2022-03-23T00:00:00Z","timestamp":1647993600000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2022,3,23]],"date-time":"2022-03-23T00:00:00Z","timestamp":1647993600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["BMC Med Genomics"],"published-print":{"date-parts":[[2022,12]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>\n                    SMG9-deficiency syndrome, also known as heart and brain malformation syndrome, is a very rare congenital genetic disorder mainly characterized by brain, heart, and growth and developmental abnormalities. This syndrome is an autosomal recessive disease resulting from mutations in the\n                    <jats:italic>SMG9<\/jats:italic>\n                    gene, which encodes a critical component of nonsense-mediated mRNA decay. Thus far, only twelve SMG9 deficiency patients have been reported with five novel homozygous\n                    <jats:italic>SMG9<\/jats:italic>\n                    mutations. The most frequent characteristic features of these patients are facial dysmorphism, severe global developmental delay, intellectual disability, congenital heart disease, growth restriction, microcephaly, and brain abnormalities. Herein, whole exome sequencing was performed to identify novel compound heterozygous\n                    <jats:italic>SMG9<\/jats:italic>\n                    variants (NM_019108.3: c.1318_1319delAG (p.Ser440*) and c.947A&gt;G (p.His316Arg)) in the proband, who exhibited syndromic intellectual disability. Mutations were confirmed as segregating in his affected sister and other unaffected family members by Sanger sequencing. The patients we describe here have a similar dysmorphology profile associated with SMG9-deficiency syndrome. Comparing the phenotype with that of patients in published reports, our patients can walk independently and their growth parameters are normal. In addition, short stature, failure to thrive, and microcephaly were not observed. Possible residual function of the H316R\n                    <jats:italic>SMG9<\/jats:italic>\n                    variant could explain the milder phenotype observed in our patients. Our report is the first description of a non-consanguineous Chinese pedigree with novel compound heterozygous variants in the SMG9 gene. The molecular confirmation of the patient expands the genetic spectrum of SMG9-deficiency syndrome, and the manifestation of SMG9-deficiency syndrome in the patient provides additional clinical information regarding this syndrome.\n                  <\/jats:p>","DOI":"10.1186\/s12920-022-01217-9","type":"journal-article","created":{"date-parts":[[2022,3,23]],"date-time":"2022-03-23T13:03:39Z","timestamp":1648040619000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":5,"title":["Identification of a novel compound heterozygous SMG9 variants in a Chinese family with heart and brain malformation syndrome using whole exome sequencing"],"prefix":"10.1186","volume":"15","author":[{"given":"Qi","family":"Yang","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zailong","family":"Qin","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qinle","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shang","family":"Yi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sheng","family":"Yi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jingsi","family":"Luo","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2022,3,23]]},"reference":[{"issue":"9","key":"1217_CR1","doi-asserted-by":"publisher","first-page":"1091","DOI":"10.1101\/gad.1767209","volume":"23","author":"A Yamashita","year":"2009","unstructured":"Yamashita A, Izumi N, Kashima I, Ohnishi T, Saari B, Katsuhata Y, Muramatsu R, Morita T, Iwamatsu A, Hachiya T, et al. SMG-8 and SMG-9, two novel subunits of the SMG-1 complex, regulate remodeling of the mRNA surveillance complex during nonsense-mediated mRNA decay. Genes Dev. 2009;23(9):1091\u2013105. https:\/\/doi.org\/10.1101\/gad.1767209.","journal-title":"Genes Dev"},{"issue":"5","key":"1217_CR2","first-page":"453","volume":"1","author":"LE Maquat","year":"1995","unstructured":"Maquat LE. When cells stop making sense: effects of nonsense codons on RNA metabolism in vertebrate cells. RNA. 1995;1(5):453\u201365.","journal-title":"RNA"},{"key":"1217_CR3","doi-asserted-by":"publisher","first-page":"139","DOI":"10.1146\/annurev-genet-111212-133424","volume":"47","author":"MW Popp","year":"2013","unstructured":"Popp MW, Maquat LE. Organizing principles of mammalian nonsense-mediated mRNA decay. Annu Rev Genet. 2013;47:139\u201365. https:\/\/doi.org\/10.1146\/annurev-genet-111212-133424.","journal-title":"Annu Rev Genet"},{"issue":"4","key":"1217_CR4","doi-asserted-by":"publisher","first-page":"467","DOI":"10.1083\/jcb.201311103","volume":"204","author":"J Lykke-Andersen","year":"2014","unstructured":"Lykke-Andersen J, Bennett EJ. Protecting the proteome: eukaryotic cotranslational quality control pathways. J Cell Biol. 2014;204(4):467\u201376. https:\/\/doi.org\/10.1083\/jcb.201311103.","journal-title":"J Cell Biol"},{"issue":"5","key":"1217_CR5","doi-asserted-by":"publisher","first-page":"661","DOI":"10.1002\/wrna.1357","volume":"7","author":"ED Karousis","year":"2016","unstructured":"Karousis ED, Nasif S, M\u00fchlemann O. Nonsense-mediated mRNA decay: novel mechanistic insights and biological impact. Wiley Interdiscip Rev RNA. 2016;7(5):661\u201382. https:\/\/doi.org\/10.1002\/wrna.1357.","journal-title":"Wiley Interdiscip Rev RNA"},{"key":"1217_CR6","doi-asserted-by":"publisher","first-page":"78","DOI":"10.1016\/j.semcdb.2017.08.053","volume":"75","author":"S Nasif","year":"2018","unstructured":"Nasif S, Contu L, M\u00fchlemann O. Beyond quality control: the role of nonsense-mediated mRNA decay (NMD) in regulating gene expression. Semin Cell Dev Biol. 2018;75:78\u201387. https:\/\/doi.org\/10.1016\/j.semcdb.2017.08.053.","journal-title":"Semin Cell Dev Biol"},{"issue":"11","key":"1217_CR7","doi-asserted-by":"publisher","first-page":"1645","DOI":"10.1038\/s41588-019-0517-5","volume":"51","author":"RGH Lindeboom","year":"2019","unstructured":"Lindeboom RGH, Vermeulen M, Lehner B, Supek F. The impact of nonsense-mediated mRNA decay on genetic disease, gene editing and cancer immunotherapy. Nat Genet. 2019;51(11):1645\u201351. https:\/\/doi.org\/10.1038\/s41588-019-0517-5.","journal-title":"Nat Genet"},{"issue":"15","key":"1217_CR8","doi-asserted-by":"publisher","first-page":"7600","DOI":"10.1093\/nar\/gkv668","volume":"43","author":"A Deniaud","year":"2015","unstructured":"Deniaud A, Karuppasamy M, Bock T, Masiulis S, Huard K, Garzoni F, Kerschgens K, Hentze MW, Kulozik AE, Beck M, et al. A network of SMG-8, SMG-9 and SMG-1 C-terminal insertion domain regulates UPF1 substrate recruitment and phosphorylation. Nucleic Acids Res. 2015;43(15):7600\u201311. https:\/\/doi.org\/10.1093\/nar\/gkv668.","journal-title":"Nucleic Acids Res"},{"issue":"4","key":"1217_CR9","doi-asserted-by":"publisher","first-page":"643","DOI":"10.1016\/j.ajhg.2016.02.010","volume":"98","author":"R Shaheen","year":"2016","unstructured":"Shaheen R, Anazi S, Ben-Omran T, Seidahmed MZ, Caddle LB, Palmer K, Ali R, Alshidi T, Hagos S, Goodwin L, et al. Mutations in SMG9, encoding an essential component of nonsense-mediated decay machinery, cause a multiple congenital anomaly syndrome in humans and mice. Am J Hum Genet. 2016;98(4):643\u201352. https:\/\/doi.org\/10.1016\/j.ajhg.2016.02.010.","journal-title":"Am J Hum Genet"},{"issue":"11","key":"1217_CR10","doi-asserted-by":"publisher","first-page":"2257","DOI":"10.1002\/ajmg.a.61317","volume":"179","author":"F Lecoquierre","year":"2019","unstructured":"Lecoquierre F, Bonnevalle A, Chadie A, Gayet C, Dumant-Forest C, Renaux-Petel M, Leca JB, Hazelzet T, Brasseur-Daudruy M, Louillet F, et al. Confirmation and further delineation of the SMG9-deficiency syndrome, a rare and severe developmental disorder. Am J Med Genet A. 2019;179(11):2257\u201362. https:\/\/doi.org\/10.1002\/ajmg.a.61317.","journal-title":"Am J Med Genet A"},{"issue":"7","key":"1217_CR11","doi-asserted-by":"publisher","first-page":"1829","DOI":"10.1002\/ajmg.a.61616","volume":"182","author":"G Lemire","year":"2020","unstructured":"Lemire G, MacDonald SK, Boycott KM. SMG9-deficiency syndrome caused by a homozygous missense variant: expanding the genotypic and phenotypic spectrum of this developmental disorder. Am J Med Genet A. 2020;182(7):1829\u201331. https:\/\/doi.org\/10.1002\/ajmg.a.61616.","journal-title":"Am J Med Genet A"},{"issue":"5","key":"1217_CR12","doi-asserted-by":"publisher","first-page":"1624","DOI":"10.1002\/ajmg.a.62139","volume":"185","author":"N Altuwaijri","year":"2021","unstructured":"Altuwaijri N, Abdelbaky M, Alhashem A, Alrakaf M, Hashem M, Alzahrani F, et al. Further delineation of SMG9-related heart and brain malformation syndrome. 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Standards and guidelines for the interpretation of sequence variants: a joint consensus recommendation of the American College of Medical Genetics and Genomics and the Association for Molecular Pathology. Genet Med. 2015;17:405\u201324.","journal-title":"Genet Med"},{"issue":"7","key":"1217_CR15","doi-asserted-by":"publisher","first-page":"1028","DOI":"10.1261\/rna.061200.117","volume":"23","author":"L Li","year":"2017","unstructured":"Li L, Lingaraju M, Basquin C, Basquin J, Conti E. Structure of a SMG8-SMG9 complex identifies a G-domain heterodimer in the NMD effector proteins. RNA. 2017;23(7):1028\u201334. https:\/\/doi.org\/10.1261\/rna.061200.117.","journal-title":"RNA"},{"issue":"12","key":"1217_CR16","doi-asserted-by":"publisher","first-page":"1089","DOI":"10.1038\/s41594-019-0342-7","volume":"26","author":"Y Gat","year":"2019","unstructured":"Gat Y, Schuller JM, Lingaraju M, Weyher E, Bonneau F, Strauss M, et al. 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Am J Hum Genet. 2020;107(6):1178\u201385. https:\/\/doi.org\/10.1016\/j.ajhg.2020.11.007.","journal-title":"Am J Hum Genet"}],"container-title":["BMC Medical Genomics"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1186\/s12920-022-01217-9.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/article\/10.1186\/s12920-022-01217-9\/fulltext.html","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1186\/s12920-022-01217-9.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2022,3,23]],"date-time":"2022-03-23T13:06:44Z","timestamp":1648040804000},"score":1,"resource":{"primary":{"URL":"https:\/\/bmcmedgenomics.biomedcentral.com\/articles\/10.1186\/s12920-022-01217-9"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,3,23]]},"references-count":18,"journal-issue":{"issue":"1","published-print":{"date-parts":[[2022,12]]}},"alternative-id":["1217"],"URL":"https:\/\/doi.org\/10.1186\/s12920-022-01217-9","relation":{},"ISSN":["1755-8794"],"issn-type":[{"value":"1755-8794","type":"electronic"}],"subject":[],"published":{"date-parts":[[2022,3,23]]},"assertion":[{"value":"18 January 2022","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"17 March 2022","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"23 March 2022","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Declarations"}},{"value":"The study was approved by the Institutional Review Board and Ethics Committee of Guangxi Maternal and Child Health Hospital. All methods were performed in accordance with the relevant guidelines and regulations of The Declaration of Helsinki. Written informed consents were obtained from participants and the parents of the participant under the age of 16.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Ethics approval and consent to participate"}},{"value":"Written informed consents for publication of clinical details and clinical images were obtained from participants and the parents of the participant under the age of 16.","order":3,"name":"Ethics","group":{"name":"EthicsHeading","label":"Consent for publication"}},{"value":"The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.","order":4,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}],"article-number":"67"}}