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Shanghai","award":["shslczdzk05705"],"award-info":[{"award-number":["shslczdzk05705"]}]},{"name":"Innovative Research Team of High-Level Local Universities in Shanghai","award":["2017ZZ02019"],"award-info":[{"award-number":["2017ZZ02019"]}]},{"name":"Innovative Research Team of High-Level Local Universities in Shanghai","award":["SHSMU-ZDCX20212200"],"award-info":[{"award-number":["SHSMU-ZDCX20212200"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Genes"],"abstract":"<jats:p>Pathogenic variants of zinc finger C4H2-type containing (ZC4H2) on the X chromosome cause a group of genetic diseases termed ZC4H2-associated rare disorders (ZARD), including Wieacker-Wolff Syndrome (WRWF) and Female-restricted Wieacker-Wolff Syndrome (WRWFFR). In the current study, a de novo c.352C&gt;T (p.Gln118*) mutation in ZC4H2 (NM_018684.4) was identified in a female neonate born with severe arthrogryposis multiplex congenita (AMC) and Pierre-Robin sequence (cleft palate and micrognathia). Plasmids containing the wild-type (WT), mutant-type (MT) ZC4H2, or GFP report gene (N) were transfected in 293T cell lines, respectively. RT-qPCR and western blot analysis showed that ZC4H2 protein could not be detected in the 293T cells transfected with MT ZC4H2. The RNA seq results revealed that the expression profile of the MT group was similar to that of the N group but differed significantly from the WT group, indicating that the c.352C&gt;T mutation resulted in the loss of function of ZC4H2. Differentially expressed genes (DEGs) enrichment analysis showed that c.352C&gt;T mutation inhibited the expression levels of a series of genes involved in the oxidative phosphorylation pathway. Subsequently, expression levels of ZC4H2 were knocked down in neural stem cells (NSCs) derived from induced pluripotent stem cells (iPSCs) by lentiviral-expressed small hairpin RNAs (shRNAs) against ZC4H2. The results also demonstrated that decreasing the expression of ZC4H2 significantly reduced the growth of NSCs by affecting the expression of genes related to the oxidative phosphorylation signaling pathway. Taken together, our results strongly suggest that ZC4H2 c.352C&gt;T (p.Gln118*) mutation resulted in the loss of protein function and caused WRWFFR.<\/jats:p>","DOI":"10.3390\/genes13091558","type":"journal-article","created":{"date-parts":[[2022,8,29]],"date-time":"2022-08-29T21:01:31Z","timestamp":1661806891000},"page":"1558","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":11,"title":["Loss of Protein Function Causing Severe Phenotypes of Female-Restricted Wieacker Wolff Syndrome due to a Novel Nonsense Mutation in the ZC4H2 Gene"],"prefix":"10.3390","volume":"13","author":[{"given":"Jing-Jing","family":"Sun","sequence":"first","affiliation":[{"name":"Shanghai Institute of Medical Genetics, Shanghai Children\u2019s Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200040, China"},{"name":"Department of Neonatology, Shanghai Children\u2019s Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200062, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qin","family":"Cai","sequence":"additional","affiliation":[{"name":"Shanghai Institute of Medical Genetics, Shanghai Children\u2019s Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200040, China"},{"name":"Department of Histo-Embryology, Genetics and Developmental Biology, Shanghai Jiao Tong University School of Medicine, Shanghai 200025, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Miao","family":"Xu","sequence":"additional","affiliation":[{"name":"Shanghai Institute of Medical Genetics, Shanghai Children\u2019s Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200040, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yan-Na","family":"Liu","sequence":"additional","affiliation":[{"name":"Shanghai Institute of Medical Genetics, Shanghai Children\u2019s Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200040, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wan-Rui","family":"Li","sequence":"additional","affiliation":[{"name":"Shanghai Institute of Medical Genetics, Shanghai Children\u2019s Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200040, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Juan","family":"Li","sequence":"additional","affiliation":[{"name":"Department of Neonatology, Shanghai Children\u2019s Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200062, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3212-0704","authenticated-orcid":false,"given":"Li","family":"Ma","sequence":"additional","affiliation":[{"name":"Department of Neonatology, Shanghai Children\u2019s Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200062, 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J. Med. Genet."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"681","DOI":"10.1016\/j.ajhg.2013.03.021","article-title":"ZC4H2 mutations are associated with arthrogryposis multiplex congenita and intellectual disability through impairment of central and peripheral synaptic plasticity","volume":"92","author":"Hirata","year":"2013","journal-title":"Am. J. Hum. Genet."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"4848","DOI":"10.1093\/hmg\/ddv208","article-title":"ZC4H2, an XLID gene, is required for the generation of a specific subset of CNS interneurons","volume":"24","author":"May","year":"2015","journal-title":"Hum. Mol. Genet."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"2270","DOI":"10.1002\/humu.23841","article-title":"Deleterious de novo variants of X-linked ZC4H2 in females cause a variable phenotype with neurogenic arthrogryposis multiplex congenita","volume":"40","author":"Frints","year":"2019","journal-title":"Hum. Mutat."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"167","DOI":"10.1002\/ajmg.a.38527","article-title":"Wieacker\u2013Wolff syndrome with associated cleft palate in a female case","volume":"176","author":"Godfrey","year":"2018","journal-title":"Am. J. Med. Genet. Part A"},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"656","DOI":"10.1007\/BF02072628","article-title":"A family with severe X-linked arthrogryposis","volume":"150","author":"Hennekam","year":"1991","journal-title":"Eur. J. Pediatrics"},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"1358","DOI":"10.1002\/ajmg.a.38155","article-title":"ZC4H2 deletions can cause severe phenotype in female carriers","volume":"173","author":"Zanzottera","year":"2017","journal-title":"Am. J. Med. Genet. Part A"},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"334","DOI":"10.1016\/j.braindev.2017.11.011","article-title":"A severe female case of arthrogryposis multiplex congenita with brain atrophy, spastic quadriplegia and intellectual disability caused by ZC4H2 mutation","volume":"40","author":"Okubo","year":"2018","journal-title":"Brain Dev."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"e1100","DOI":"10.1002\/mgg3.1100","article-title":"A novel de novo nonsense mutation in ZC4H2 causes Wieacker-Wolff Syndrome","volume":"8","author":"Wang","year":"2020","journal-title":"Mol. Genet. Genom. Med."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"612","DOI":"10.1080\/13816810.2021.1923040","article-title":"A 7-year old female with arthrogryposis multiplex congenita, Duane retraction syndrome, and Marcus Gunn phenomenon due to a ZC4H2 gene mutation: A clinical presentation of the Wieacker-Wolff syndrome","volume":"42","author":"Godfrey","year":"2021","journal-title":"Ophthalmic Genet."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"e04718","DOI":"10.1002\/ccr3.4718","article-title":"Wieacker-Wolff syndrome, a distinctive phenotype of arthrogryposis multiplex congenita caused by a \u201cde novo\u201d ZC4H2 gene partial deletion","volume":"9","author":"Deneufbourg","year":"2021","journal-title":"Clin. Case Rep."},{"key":"ref_12","doi-asserted-by":"crossref","unstructured":"Vangeel, L., Janssens, A., Lemmens, I., Lievens, S., Tavernier, J., and Voets, T. (2020). The Zinc-Finger Domain Containing Protein ZC4H2 Interacts with TRPV4, Enhancing Channel Activity and Turnover at the Plasma Membrane. Int. J. Mol. Sci., 21.","DOI":"10.3390\/ijms21103556"},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"dev165340","DOI":"10.1242\/dev.165340","article-title":"Rnf220 cooperates with Zc4h2 to specify spinal progenitor domains","volume":"145","author":"Kim","year":"2018","journal-title":"Development"},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"dev185199","DOI":"10.1242\/dev.185199","article-title":"Rnf220\/Zc4h2-mediated monoubiquitylation of Phox2 is required for noradrenergic neuron development","volume":"147","author":"Song","year":"2020","journal-title":"Development"},{"key":"ref_15","doi-asserted-by":"crossref","unstructured":"Skierka, A.S., and Michels, K.B. (2018). Ethical principles and placebo-controlled trials\u2014Interpretation and implementation of the Declaration of Helsinki\u2019s placebo paragraph in medical research. BMC Med. Ethics, 19.","DOI":"10.1186\/s12910-018-0262-9"},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"1014","DOI":"10.1111\/brv.12383","article-title":"Identification of de novo germline mutations and causal genes for sporadic diseases using trio-based whole-exome\/genome sequencing","volume":"93","author":"Jin","year":"2018","journal-title":"Biol. Rev. Camb. Philos. Soc."},{"key":"ref_17","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_18","doi-asserted-by":"crossref","first-page":"49","DOI":"10.1007\/s004390050909","article-title":"A new assay for the analysis of X-chromosome inactivation based on methylation-specific PCR","volume":"104","author":"Kubota","year":"1999","journal-title":"Hum. Genet."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"D306","DOI":"10.1093\/nar\/gkr948","article-title":"InterPro in 2011: New developments in the family and domain prediction database","volume":"40","author":"Hunter","year":"2012","journal-title":"Nucleic Acids Res."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"284","DOI":"10.1089\/omi.2011.0118","article-title":"clusterProfiler: An R package for comparing biological themes among gene clusters","volume":"16","author":"Yu","year":"2012","journal-title":"OMICS"},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"402","DOI":"10.1006\/meth.2001.1262","article-title":"Analysis of relative gene expression data using real-time quantitative PCR and the 2(-Delta Delta C(T)) Method","volume":"25","author":"Livak","year":"2001","journal-title":"Methods"},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"434","DOI":"10.1038\/s41586-020-2308-7","article-title":"The mutational constraint spectrum quantified from variation in 141,456 humans","volume":"581","author":"Karczewski","year":"2020","journal-title":"Nature"},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"W535","DOI":"10.1093\/nar\/gkab354","article-title":"PredictProtein\u2014Predicting Protein Structure and Function for 29 Years","volume":"49","author":"Bernhofer","year":"2021","journal-title":"Nucleic Acids Res."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"2428","DOI":"10.1016\/j.jmb.2020.02.026","article-title":"ProNA2020 predicts protein-DNA, protein-RNA, and protein-protein binding proteins and residues from sequence","volume":"432","author":"Qiu","year":"2020","journal-title":"J. Mol. Biol."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"215","DOI":"10.1002\/ajmg.1320380209","article-title":"Unique X-linked mental retardation syndrome with fingertip arches and contractures linked to Xq21.31","volume":"38","author":"Miles","year":"1991","journal-title":"Am. J. Med. Genet."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"760","DOI":"10.1016\/j.braindev.2018.05.003","article-title":"A novel ZC4H2 gene mutation, K209N, in Japanese siblings with arthrogryposis multiplex congenita and intellectual disability: Characterization of the K209N mutation and clinical findings","volume":"40","author":"Kondo","year":"2018","journal-title":"Brain Dev."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"985","DOI":"10.1111\/ped.14211","article-title":"A case report of rare ZC4H2-associated disorders associated with three large hernias","volume":"62","author":"Nagara","year":"2020","journal-title":"Pediatr. Int."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"704747","DOI":"10.3389\/fneur.2021.704747","article-title":"Neuromuscular and Neuroendocrinological Features Associated with ZC4H2-Related Arthrogryposis Multiplex Congenita in a Sicilian Family: A Case Report","volume":"12","author":"Piccolo","year":"2021","journal-title":"Front. Neurol."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"78","DOI":"10.1016\/j.semcdb.2016.03.009","article-title":"X inactivation and reactivation in X-linked diseases","volume":"56","author":"Vacca","year":"2016","journal-title":"Semin. Cell Dev. Biol."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"257","DOI":"10.1007\/s12640-018-9942-y","article-title":"Mitochondria in Developmental and Adult Neurogenesis","volume":"36","author":"Andraini","year":"2019","journal-title":"Neurotox. Res."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"247","DOI":"10.3389\/fnagi.2020.00247","article-title":"Stem Cells of the Aging Brain","volume":"12","author":"Nicaise","year":"2020","journal-title":"Front. Aging Neurosci."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"1795","DOI":"10.1016\/j.celrep.2013.05.005","article-title":"NDUFA4 mutations underlie dysfunction of a cytochrome c oxidase subunit linked to human neurological disease","volume":"3","author":"Pitceathly","year":"2013","journal-title":"Cell Rep."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"159","DOI":"10.1038\/ejhg.2014.85","article-title":"Mitochondrial complex IV deficiency, caused by mutated COX6B1, is associated with encephalomyopathy, hydrocephalus and cardiomyopathy","volume":"23","author":"Abdulhag","year":"2015","journal-title":"Eur. J. Hum. Genet."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"1281","DOI":"10.1016\/j.ajhg.2008.05.002","article-title":"Severe infantile encephalomyopathy caused by a mutation in COX6B1, a nucleus-encoded subunit of cytochrome c oxidase","volume":"82","author":"Massa","year":"2008","journal-title":"Am. J. Hum. Genet."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"294","DOI":"10.1016\/j.ajhg.2014.07.013","article-title":"A mutation of COX6A1 causes a recessive axonal or mixed form of Charcot-Marie-Tooth disease","volume":"95","author":"Tamiya","year":"2014","journal-title":"Am. J. Hum. Genet."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"338","DOI":"10.1093\/brain\/awv357","article-title":"Loss of the smallest subunit of cytochrome c oxidase, COX8A, causes Leigh-like syndrome and epilepsy","volume":"139","author":"Rotko","year":"2016","journal-title":"Brain"},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"e00021","DOI":"10.1042\/BSR20120097","article-title":"Dihydro-orotate dehydrogenase is physically associated with the respiratory complex and its loss leads to mitochondrial dysfunction","volume":"33","author":"Fang","year":"2013","journal-title":"Biosci. Rep."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"2605","DOI":"10.1242\/dev.040048","article-title":"Molecular mechanisms of cranial neural crest cell migration and patterning in craniofacial development","volume":"137","author":"Minoux","year":"2010","journal-title":"Development"}],"container-title":["Genes"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2073-4425\/13\/9\/1558\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T00:19:54Z","timestamp":1760141994000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2073-4425\/13\/9\/1558"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,8,29]]},"references-count":38,"journal-issue":{"issue":"9","published-online":{"date-parts":[[2022,9]]}},"alternative-id":["genes13091558"],"URL":"https:\/\/doi.org\/10.3390\/genes13091558","relation":{},"ISSN":["2073-4425"],"issn-type":[{"value":"2073-4425","type":"electronic"}],"subject":[],"published":{"date-parts":[[2022,8,29]]}}}