{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,1,13]],"date-time":"2026-01-13T05:24:26Z","timestamp":1768281866741,"version":"3.49.0"},"reference-count":24,"publisher":"Wiley","issue":"2","license":[{"start":{"date-parts":[[2019,12,30]],"date-time":"2019-12-30T00:00:00Z","timestamp":1577664000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001804","name":"Canada Research Chairs","doi-asserted-by":"crossref","id":[{"id":"10.13039\/501100001804","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Molec Gen &amp;amp; Gen Med"],"published-print":{"date-parts":[[2020,2]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Background<\/jats:title><jats:p>Wieacker\u2010Wolff syndrome (WWS) is a congenital X\u2010linked neuromuscular disorder, which was firstly reported in 1985. Zinc finger C4H2\u2010type containing (<jats:italic>ZC4H2<\/jats:italic>) gene has been found to be associated with the disease pathogenesis. However, the underlying mechanism remains elusive.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Whole\u2010exome sequencing was performed to identify the mutations. Expression plasmids were constructed and cell culture and immune\u2010biochemical assays were used to examine the effects of the mutation.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>We reported a female patient with classical symptoms of WWS and discovered a novel nonsense heterozygous mutation (p.R67X; c.199C&gt;T) in <jats:italic>ZC4H2<\/jats:italic> gene in the patient but not in her parents. The mutation resulted in a 66 amino\u2010acid truncated ZC4H2 protein. The mutation is located in the key helix domain and it altered the subcellular locations of the mutant ZC4H2 protein. X\u2010chromosome inactivation (XCI) pattern analysis revealed that the XCI ratio of the proband was 22:78.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>Female heterozygous carriers with nonsense mutation with a truncated ZC4H2 protein could lead to the pathogenesis of Wieacker\u2010Wolff syndrome and our study provides a potential new target for the disease treatment.<\/jats:p><\/jats:sec>","DOI":"10.1002\/mgg3.1100","type":"journal-article","created":{"date-parts":[[2019,12,30]],"date-time":"2019-12-30T09:43:18Z","timestamp":1577698998000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":13,"title":["A novel de novo nonsense mutation in <i>ZC4H2<\/i> causes Wieacker\u2010Wolff Syndrome"],"prefix":"10.1002","volume":"8","author":[{"given":"Dan","family":"Wang","sequence":"first","affiliation":[{"name":"Chongqing City Key Lab of Translational Medical Research in Cognitive Development and Learning and Memory Disorders, and Ministry of Education Key Lab of Child Development and Disorders Children\u2019s Hospital of Chongqing Medical University Chongqing China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Dongjie","family":"Hu","sequence":"additional","affiliation":[{"name":"Chongqing City Key Lab of Translational Medical Research in Cognitive Development and Learning and Memory Disorders, and Ministry of Education Key Lab of Child Development and Disorders Children\u2019s Hospital of Chongqing Medical University Chongqing China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Zhichao","family":"Guo","sequence":"additional","affiliation":[{"name":"Department of Internal Neurology Children\u2019s Hospital of Chongqing Medical University Chongqing China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Rong","family":"Hu","sequence":"additional","affiliation":[{"name":"Chongqing City Key Lab of Translational Medical Research in 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