{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,15]],"date-time":"2026-08-15T04:29:20Z","timestamp":1786768160441,"version":"build-2736575974"},"reference-count":21,"publisher":"MDPI AG","issue":"8","license":[{"start":{"date-parts":[[2026,8,13]],"date-time":"2026-08-13T00:00:00Z","timestamp":1786579200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"The Key Research and Development Program of Zhejiang","award":["2024C03151"],"award-info":[{"award-number":["2024C03151"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Genes"],"abstract":"<jats:p>Background: Pathogenic variants in ZNF292 cause intellectual disability type 64 (MIM#619188), characterized by intellectual impairment ranging from mild to severe, speech delay, and autism spectrum disorder. However, reports of ZNF292-related neurodevelopmental disorders remain scarce, and most published studies are based on multi-center cohorts. Methods: We performed whole-exome sequencing in eight unrelated individuals presenting with unexplained neurodevelopmental disorders, including global developmental delay and\/or intellectual disability. Detailed clinical characterization, neuroimaging, and developmental assessments were conducted. Results: Seven de novo variants in ZNF292 were identified, including two nonsense and five frameshift variants, namely, c.4189C&gt;T (p.Arg1397Ter), c.6343C&gt;T (p.Arg2115Ter), c.1533del (p.Ile511Metfs*11), c.3094dup (p.Ser1032Phefs*18), c.3997_3998del (p.Thr1333Glnfs*8), c.6028_6031del (p.Ala2010Ter) and c.6160_6161del (p.Glu2054Lysfs*14). Among these, c.1533del (p.Ile511Metfs11), c.3094dup (p.Ser1032Phefs18) and c.3997_3998del (p.Thr1333Glnfs*8) are reported here for the first time. All variants were classified as pathogenic. All individuals exhibited global developmental delay, intellectual disability, and short stature. The majority presented with language impairment, motor delays, autism spectrum features, and dysmorphic facial features, while brain magnetic resonance imaging revealed nonspecific abnormalities such as ventriculomegaly. Conclusions: This study contributes additional cases to the expanding phenotypic and mutational spectrum of ZNF292-related neurodevelopmental disorder. Growth retardation was observed in all eight individuals, but given the limitations of a single-center referral cohort, this observation should be interpreted with caution and requires validation in larger studies.<\/jats:p>","DOI":"10.3390\/genes17080950","type":"journal-article","created":{"date-parts":[[2026,8,13]],"date-time":"2026-08-13T17:01:35Z","timestamp":1786640495000},"page":"950","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["De Novo\u00a0ZNF292 Variants Cause Neurodevelopmental Disorder with Short Stature: A Clinical Case Series of Eight Individuals"],"prefix":"10.3390","volume":"17","author":[{"given":"Yaping","family":"Shen","sequence":"first","affiliation":[{"name":"Department of Genetics and Metabolism, Children\u2019s Hospital, Zhejiang University School of Medicine, National Clinical Research Center for Children and Adolescents\u2019 Health and Disease, Hangzhou 310052, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rongrong","family":"Pan","sequence":"additional","affiliation":[{"name":"Department of Genetics and Metabolism, Children\u2019s Hospital, Zhejiang University School of Medicine, National Clinical Research Center for Children and Adolescents\u2019 Health and Disease, Hangzhou 310052, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8009-7978","authenticated-orcid":false,"given":"Chen","family":"Liu","sequence":"additional","affiliation":[{"name":"Department of Genetics and Metabolism, Children\u2019s Hospital, Zhejiang University School of Medicine, National Clinical Research Center for Children and Adolescents\u2019 Health and Disease, Hangzhou 310052, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jing","family":"Zheng","sequence":"additional","affiliation":[{"name":"Department of Genetics and Metabolism, Children\u2019s Hospital, Zhejiang University School of Medicine, National Clinical Research Center for Children and Adolescents\u2019 Health and Disease, Hangzhou 310052, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4267-9579","authenticated-orcid":false,"given":"Xin","family":"Yang","sequence":"additional","affiliation":[{"name":"Department of Genetics and Metabolism, Children\u2019s Hospital, Zhejiang University School of Medicine, National Clinical Research Center for Children and Adolescents\u2019 Health and Disease, Hangzhou 310052, China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,8,13]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"538","DOI":"10.1038\/s41436-019-0693-9","article-title":"De novo and inherited variants in ZNF292 underlie a neurodevelopmental disorder with features of autism spectrum disorder","volume":"22","author":"Mirzaa","year":"2020","journal-title":"Genet. Med."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"115597","DOI":"10.1016\/j.celrep.2025.115597","article-title":"Requirements for the neurodevelopmental disorder-associated gene ZNF292 in human cortical interneuron development and function","volume":"44","author":"Kaushik","year":"2025","journal-title":"Cell Rep."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"405","DOI":"10.1038\/gim.2015.30","article-title":"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","volume":"17","author":"Richards","year":"2015","journal-title":"Genet. Med."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"1320","DOI":"10.1038\/s41588-022-01104-0","article-title":"Rare coding variation provides insight into the genetic architecture and phenotypic context of autism","volume":"54","author":"Fu","year":"2022","journal-title":"Nat. Genet."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"359","DOI":"10.1007\/s00431-021-04213-w","article-title":"Congenital anomalies and genetic disorders in neonates and infants: A single-center observational cohort study","volume":"181","author":"Marouane","year":"2022","journal-title":"Eur. J. Pediatr."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"1921","DOI":"10.1056\/NEJMoa1206524","article-title":"Diagnostic exome sequencing in persons with severe intellectual disability","volume":"367","author":"Willemsen","year":"2012","journal-title":"N. Engl. J. Med."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"209","DOI":"10.1038\/nature13772","article-title":"Synaptic, transcriptional and chromatin genes disrupted in autism","volume":"515","author":"He","year":"2014","journal-title":"Nature"},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"13316","DOI":"10.1038\/ncomms13316","article-title":"De novo genic mutations among a Chinese autism spectrum disorder cohort","volume":"7","author":"Wang","year":"2016","journal-title":"Nat. Commun."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"64","DOI":"10.1186\/s13229-018-0247-z","article-title":"Inherited and multiple de novo mutations in autism\/developmental delay risk genes suggest a multifactorial model","volume":"9","author":"Guo","year":"2018","journal-title":"Mol. Autism"},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"e70747","DOI":"10.1002\/ccr3.70747","article-title":"Short Stature and Developmental Delay Associated with a Novel Frame-Shift Mutation in ZNF292: Case Report and Literature Review","volume":"13","author":"Li","year":"2025","journal-title":"Clin. Case Rep."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"1364","DOI":"10.1038\/s41431-017-0022-1","article-title":"Exome Pool-Seq in neurodevelopmental disorders","volume":"25","author":"Popp","year":"2017","journal-title":"Eur. J. Hum. Genet."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"1551","DOI":"10.1038\/s41436-021-01159-0","article-title":"Combining exome\/genome sequencing with data repository analysis reveals novel gene-disease associations for a wide range of genetic disorders","volume":"23","author":"Kandaswamy","year":"2021","journal-title":"Genet. Med."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"351","DOI":"10.1007\/s00439-022-02509-x","article-title":"Targeting de novo loss-of-function variants in constrained disease genes improves diagnostic rates in the 100,000 Genomes Project","volume":"142","author":"Seaby","year":"2023","journal-title":"Hum. Genet."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"101202","DOI":"10.1016\/j.gim.2024.101202","article-title":"Return of genetic research results in 21,532 individuals with autism","volume":"26","author":"Wright","year":"2024","journal-title":"Genet. Med."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"1644","DOI":"10.1038\/s41588-024-01836-1","article-title":"Next-generation phenotyping integrated in a national framework for patients with ultrarare disorders improves genetic diagnostics and yields new molecular findings","volume":"56","author":"Schmidt","year":"2024","journal-title":"Nat. Genet."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"278","DOI":"10.1111\/cge.14649","article-title":"Diagnostic Use of Genome Sequencing in Patients with 11p15.5 Imprinting Disorder Features: A Pilot Study","volume":"107","author":"Kessler","year":"2025","journal-title":"Clin. Genet."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"13","DOI":"10.1038\/s41525-022-00284-2","article-title":"Analysis of recent shared ancestry in a familial cohort identifies coding and noncoding autism spectrum disorder variants","volume":"7","author":"Tuncay","year":"2022","journal-title":"npj Genom. Med."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"10","DOI":"10.1186\/s13229-025-00642-8","article-title":"Deciphering the genetic basis of developmental language disorder in children without intellectual disability, autism or apraxia of speech","volume":"16","author":"Ormieres","year":"2025","journal-title":"Mol. Autism"},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"556","DOI":"10.1111\/apm.12545","article-title":"Frameshift mutations of a tumor suppressor gene ZNF292 in gastric and colorectal cancers with high microsatellite instability","volume":"124","author":"Lee","year":"2016","journal-title":"APMIS"},{"key":"ref_20","doi-asserted-by":"crossref","unstructured":"Camacho, N., Van Loo, P., Edwards, S., Kay, J.D., Matthews, L., Haase, K., Clark, J., Dennis, N., Thomas, S., and Kremeyer, B. (2017). Appraising the relevance of DNA copy number loss and gain in prostate cancer using whole genome DNA sequence data. PLoS Genet., 13.","DOI":"10.1371\/journal.pgen.1007001"},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"519","DOI":"10.1038\/nature14666","article-title":"Non-coding recurrent mutations in chronic lymphocytic leukaemia","volume":"526","author":"Puente","year":"2015","journal-title":"Nature"}],"container-title":["Genes"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2073-4425\/17\/8\/950\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,8,15]],"date-time":"2026-08-15T04:18:22Z","timestamp":1786767502000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2073-4425\/17\/8\/950"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,8,13]]},"references-count":21,"journal-issue":{"issue":"8","published-online":{"date-parts":[[2026,8]]}},"alternative-id":["genes17080950"],"URL":"https:\/\/doi.org\/10.3390\/genes17080950","relation":{},"ISSN":["2073-4425"],"issn-type":[{"value":"2073-4425","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,8,13]]}}}