Identification of novel RIPK4 variants in a Chinese patient with Arthrogryposis Multiplex Congenita (AMC)
Abstract Background Arthrogryposis multiplex congenita (AMC) is a congenital disorder characterized by multiple joint involvement, primarily affecting limb mobility and leading to various tissue contractures. Variations in the RIPK4 gene may impact connective tissues, thereby resulting in a spectrum...
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| Main Authors: | , , , |
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| Format: | Article |
| Language: | English |
| Published: |
BMC
2025-01-01
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| Series: | Italian Journal of Pediatrics |
| Subjects: | |
| Online Access: | https://doi.org/10.1186/s13052-025-01858-3 |
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| Summary: | Abstract Background Arthrogryposis multiplex congenita (AMC) is a congenital disorder characterized by multiple joint involvement, primarily affecting limb mobility and leading to various tissue contractures. Variations in the RIPK4 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. Methods 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’s disease. The pathogenic mechanisms of the identified variations were analyzed using protein tolerance profiling and modeling. Results We identified two novel RIPK4 variants (c.1354G > A, p.E452K; c.1558A > T, p.T520S). Pathogenicity studies indicated that the c.1354G > A, p.E452K variant changed the charge from negative to positive and altered the chemical properties from acidic to alkaline, potentially significantly affecting protein function. Conclusions We reported the discovery of two novel RIPK4 variants (c.1354G > A, p.E452K; c.1558A > T, p.T520S) in a Chinese AMC female patient’s family. Our study enhances the genetic repository for AMC and highlights the pathogenicity of RIPK4 variants, underscoring the significance of comprehensive management for genetic-related diseases, particularly the critical roles of prenatal diagnosis and genetic counseling. Trial registration 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. |
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| ISSN: | 1824-7288 |