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Variations in the <jats:italic>RIPK4<\/jats:italic> gene may impact connective tissues, thereby resulting in a spectrum of malformations. This study aimed to identify the genetic etiologies of AMC patients and provide genetic testing information for further diagnosis and treatment of AMC.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Methods<\/jats:title>\n            <jats:p>We recruited a Chinese female patient with hand-related AMC and her family members. Whole-exome sequencing (WES) was employed to determine the genetic etiologies of the patient\u2019s disease. The pathogenic mechanisms of the identified variations were analyzed using protein tolerance profiling and modeling.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Results<\/jats:title>\n            <jats:p>We identified two novel <jats:italic>RIPK4<\/jats:italic> variants (c.1354G\u2009&gt;\u2009A, p.E452K; c.1558A\u2009&gt;\u2009T, p.T520S). Pathogenicity studies indicated that the c.1354G\u2009&gt;\u2009A, p.E452K variant changed the charge from negative to positive and altered the chemical properties from acidic to alkaline, potentially significantly affecting protein function.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Conclusions<\/jats:title>\n            <jats:p>We reported the discovery of two novel <jats:italic>RIPK4<\/jats:italic> variants (c.1354G\u2009&gt;\u2009A, p.E452K; c.1558A\u2009&gt;\u2009T, p.T520S) in a Chinese AMC female patient\u2019s family. Our study enhances the genetic repository for AMC and highlights the pathogenicity of <jats:italic>RIPK4<\/jats:italic> variants, underscoring the significance of comprehensive management for genetic-related diseases, particularly the critical roles of prenatal diagnosis and genetic counseling.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Trial registration<\/jats:title>\n            <jats:p>The research protocol received approval from the Ethics Review Committee of Xiangya Hospital of Central South University in China (approval number: 202103427), registered in March 2021, with all participants providing duly signed informed consent forms.<\/jats:p>\n          <\/jats:sec>","DOI":"10.1186\/s13052-025-01858-3","type":"journal-article","created":{"date-parts":[[2025,1,21]],"date-time":"2025-01-21T01:44:15Z","timestamp":1737423855000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Identification of novel RIPK4 variants in a Chinese patient with Arthrogryposis Multiplex Congenita (AMC)"],"prefix":"10.1186","volume":"51","author":[{"given":"Yi-Lei","family":"Lu","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Meng-wei","family":"Liu","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jie-Yuan","family":"Jin","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ding","family":"Pan","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"297","published-online":{"date-parts":[[2025,1,21]]},"reference":[{"issue":"1","key":"1858_CR1","doi-asserted-by":"publisher","first-page":"48","DOI":"10.1007\/s11684-017-0500-4","volume":"11","author":"L Ma","year":"2017","unstructured":"Ma L, Yu X. 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All methods were performed in accordance with the ethical standards as laid down in the Declaration of Helsinki and its later amendments or comparable ethical standards.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Ethics approval and consent to participate"}},{"value":"Written informed consent for publication was obtained.","order":3,"name":"Ethics","group":{"name":"EthicsHeading","label":"Consent for publication"}},{"value":"The author declares that he has no competing interests.","order":4,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}],"article-number":"6"}}