{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,24]],"date-time":"2026-10-24T06:50:22Z","timestamp":1792824622195,"version":"4.5.0"},"reference-count":10,"publisher":"Wiley","issue":"2","license":[{"start":{"date-parts":[[2024,2,26]],"date-time":"2024-02-26T00:00:00Z","timestamp":1708905600000},"content-version":"vor","delay-in-days":25,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Molec Gen &amp;amp; Gen Med"],"published-print":{"date-parts":[[2024,2]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Background<\/jats:title><jats:p>TNRC6B deficiency syndrome, also known as global developmental delay with speech and behavioral abnormalities (MIM 619243), is a rare autosomal dominant genetic disease mainly characterized by facial dysmorphism, developmental delay\/intellectual disability (DD\/ID), speech and language delay, fine and motor delay, attention deficit and hyperactivity disorder (ADHD), and variable behavioral abnormalities. It is caused by heterozygous variant in the <jats:italic>TNRC6B<\/jats:italic> gene (NM_001162501.2, MIM 610740), which encodes the trinucleotide repeat\u2010containing adaptor 6B protein.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>In this study, two Chinese patients with TNRC6B deficiency syndrome were recruited, and genomic DNA extraction from peripheral blood leukocytes of these parents and their family members was extracted for whole\u2010exome sequencing and Sanger sequencing.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Here, we report two unrelated Chinese patients diagnosed with TNRC6B deficiency syndrome caused by novel de novo likely pathogenic or pathogenic <jats:italic>TNRC6B<\/jats:italic> variants c.335C&gt;T (p.Pro112Leu) and c.1632delC (p.Leu546fs*63), which expands the genetic spectrum of TNRC6B deficiency syndrome. The clinical features of the patients were DD\/ID, delayed speech, ADHD, behavioral abnormalities, short stature, low body weight, caf\u00e9\u2010au\u2010lait spots, metabolic abnormalities, and facial dysmorphism including coarse facial features, sparse hair, frontal bossing, hypertelorism, amblyopia, strabismus, and downslanted palpebral fissures, which expands the phenotype spectrum associated with TNRC6B deficiency syndrome.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>This study expands the genotypic and phenotypic spectrum of TNRC6B deficiency syndrome. Our findings indicate that patients with TNRC6B deficiency syndrome should be monitored for growth and metabolic problems and therapeutic strategies should be developed to address these problems. Our report also suggests the clinical diversity of TNRC6B deficiency syndrome.<\/jats:p><\/jats:sec>","DOI":"10.1002\/mgg3.2408","type":"journal-article","created":{"date-parts":[[2024,2,26]],"date-time":"2024-02-26T09:10:27Z","timestamp":1708938627000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":5,"title":["Novel variants in <i>TNRC6B<\/i> cause global developmental delay with speech and behavioral abnormalities, short stature, low body weight, caf\u00e9\u2010au\u2010lait spots, and metabolic abnormality"],"prefix":"10.1002","volume":"12","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-1849-0100","authenticated-orcid":false,"given":"Qi","family":"Yang","sequence":"first","affiliation":[{"name":"Guangxi Key Laboratory of Birth Defects Research and Prevention, Guangxi Key Laboratory of Reproductive Health and Birth Defects Prevention Maternal and Child Health Hospital of Guangxi Zhuang Autonomous Region  Nanning China"},{"name":"Department of Genetic and Metabolic Central Laboratory Maternal and Child Health Hospital of Guangxi Zhuang Autonomous Region  Nanning China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shan","family":"Ou","sequence":"additional","affiliation":[{"name":"Guangxi Key Laboratory of Birth Defects Research and Prevention, Guangxi Key Laboratory of Reproductive Health and Birth Defects Prevention Maternal and Child Health Hospital of Guangxi Zhuang Autonomous Region  Nanning China"},{"name":"Department of Genetic and Metabolic Central Laboratory Maternal and Child Health Hospital of Guangxi Zhuang Autonomous Region  Nanning China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xunzhao","family":"Zhou","sequence":"additional","affiliation":[{"name":"Guangxi Key Laboratory of Birth Defects Research and Prevention, Guangxi Key Laboratory of Reproductive Health and Birth Defects Prevention Maternal and Child Health Hospital of Guangxi Zhuang Autonomous Region  Nanning China"},{"name":"Department of Genetic and Metabolic Central Laboratory Maternal and Child Health Hospital of Guangxi Zhuang Autonomous Region  Nanning China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2130-7701","authenticated-orcid":false,"given":"Sheng","family":"Yi","sequence":"additional","affiliation":[{"name":"Guangxi Key Laboratory of Birth Defects Research and Prevention, Guangxi Key Laboratory of Reproductive Health and Birth Defects Prevention Maternal and Child Health Hospital of Guangxi Zhuang Autonomous Region  Nanning China"},{"name":"Department of Genetic and Metabolic Central Laboratory Maternal and Child Health Hospital of Guangxi Zhuang Autonomous Region  Nanning China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Li","family":"Lin","sequence":"additional","affiliation":[{"name":"Guangxi Key Laboratory of Birth Defects Research and Prevention, Guangxi Key Laboratory of Reproductive Health and Birth Defects Prevention Maternal and Child Health Hospital of Guangxi Zhuang Autonomous Region  Nanning China"},{"name":"Department of Genetic and Metabolic Central Laboratory Maternal and Child Health Hospital of Guangxi Zhuang Autonomous Region  Nanning China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shang","family":"Yi","sequence":"additional","affiliation":[{"name":"Guangxi Key Laboratory of Birth Defects Research and Prevention, Guangxi Key Laboratory of Reproductive Health and Birth Defects Prevention Maternal and Child Health Hospital of Guangxi Zhuang Autonomous Region  Nanning China"},{"name":"Department of Genetic and Metabolic Central Laboratory Maternal and Child Health Hospital of Guangxi Zhuang Autonomous Region  Nanning China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shujie","family":"Zhang","sequence":"additional","affiliation":[{"name":"Guangxi Key Laboratory of Birth Defects Research and Prevention, Guangxi Key Laboratory of Reproductive Health and Birth Defects Prevention Maternal and Child Health Hospital of Guangxi Zhuang Autonomous Region  Nanning China"},{"name":"Department of Genetic and Metabolic Central Laboratory Maternal and Child Health Hospital of Guangxi Zhuang Autonomous Region  Nanning China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zailong","family":"Qin","sequence":"additional","affiliation":[{"name":"Guangxi Key Laboratory of Birth Defects Research and Prevention, Guangxi Key Laboratory of Reproductive Health and Birth Defects Prevention Maternal and Child Health Hospital of Guangxi Zhuang Autonomous Region  Nanning China"},{"name":"Department of Genetic and Metabolic Central Laboratory Maternal and Child Health Hospital of Guangxi Zhuang Autonomous Region  Nanning China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jingsi","family":"Luo","sequence":"additional","affiliation":[{"name":"Guangxi Key Laboratory of Birth Defects Research and Prevention, Guangxi Key Laboratory of Reproductive Health and Birth Defects Prevention Maternal and Child Health Hospital of Guangxi Zhuang Autonomous Region  Nanning China"},{"name":"Department of Genetic and Metabolic Central Laboratory Maternal and Child Health Hospital of Guangxi Zhuang Autonomous Region  Nanning China"},{"name":"Guangxi Clinical Research Center for Pediatric Diseases Maternal and Child Health Hospital of Guangxi Zhuang Autonomous Region  Nanning 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