Case Report: Cabezas syndrome caused by CUL4B gene mutations in two unrelated Chinese boys
As a component of the ubiquitin ligase complex, Cullin 4B (CUL4B) is involved in the process of ubiquitination of different substrates, controlling genome stability, nucleotide excision repair, and chromatin-remodeling. The mutations in the CUL4B gene are revealed to be a cause of Cabezas syndrome (...
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Frontiers Media S.A.
2025-07-01
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| Series: | Frontiers in Neuroscience |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fnins.2025.1600852/full |
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| author | Li Lin Li Lin Qi Yang Qi Yang Shujie Zhang Shujie Zhang Xunzhao Zhou Xunzhao Zhou Xiaoling Li Sheng Yi Sheng Yi Qiang Zhang Qiang Zhang Shang Yi Shang Yi Sheng He Sheng He Zailong Qin Zailong Qin Jingsi Luo Jingsi Luo Jingsi Luo |
| author_facet | Li Lin Li Lin Qi Yang Qi Yang Shujie Zhang Shujie Zhang Xunzhao Zhou Xunzhao Zhou Xiaoling Li Sheng Yi Sheng Yi Qiang Zhang Qiang Zhang Shang Yi Shang Yi Sheng He Sheng He Zailong Qin Zailong Qin Jingsi Luo Jingsi Luo Jingsi Luo |
| author_sort | Li Lin |
| collection | DOAJ |
| description | As a component of the ubiquitin ligase complex, Cullin 4B (CUL4B) is involved in the process of ubiquitination of different substrates, controlling genome stability, nucleotide excision repair, and chromatin-remodeling. The mutations in the CUL4B gene are revealed to be a cause of Cabezas syndrome (OMIM 300354), a rare syndromic form of X-linked intellectual disability (XLID). In this study, whole-exome sequencing analysis and Sanger sequencing identified two maternally inherited likely pathogenetic variants (CUL4B, NM_001079872.2: c.803dupT/p. Leu268fs*5; c.953_957delTTATA/p. Ile318fs*2) in two probands, respectively. Patients carrying CUL4B variants presented with broad and variable phenotypic defects. The clinical manifestations of the two boys are consistent with Cabezas syndrome; however, they exhibit significant heterogeneity compared to previously reported cases. Phenotypic manifestations resulting from genetic variations may exhibit population differences and, in some cases, may present with concealed or latent expressions. Therefore, regular pediatric health check-ups and appropriate molecular diagnostic techniques are essential for the early detection, diagnosis, and treatment of such disorders. Our findings could be used to better define the genetic map in this area and will be valuable in the genetic diagnosis of the disease. |
| format | Article |
| id | doaj-art-dbc1739f3681412d9f57532bb7225e8b |
| institution | Matheson Library |
| issn | 1662-453X |
| language | English |
| publishDate | 2025-07-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Neuroscience |
| spelling | doaj-art-dbc1739f3681412d9f57532bb7225e8b2025-07-21T05:21:48ZengFrontiers Media S.A.Frontiers in Neuroscience1662-453X2025-07-011910.3389/fnins.2025.16008521600852Case Report: Cabezas syndrome caused by CUL4B gene mutations in two unrelated Chinese boysLi Lin0Li Lin1Qi Yang2Qi Yang3Shujie Zhang4Shujie Zhang5Xunzhao Zhou6Xunzhao Zhou7Xiaoling Li8Sheng Yi9Sheng Yi10Qiang Zhang11Qiang Zhang12Shang Yi13Shang Yi14Sheng He15Sheng He16Zailong Qin17Zailong Qin18Jingsi Luo19Jingsi Luo20Jingsi Luo21Guangxi Clinical Research Center for Birth Defects, Guangxi Key Laboratory of Reproductive Health and Birth Defects Prevention, Maternal and Child Health Hospital of Guangxi Zhuang Autonomous Region, Nanning, ChinaDepartment of Genetic and Metabolic Central Laboratory, Maternal and Child Health Hospital of Guangxi Zhuang Autonomous Region, Nanning, ChinaGuangxi Clinical Research Center for Birth Defects, Guangxi Key Laboratory of Reproductive Health and Birth Defects Prevention, Maternal and Child Health Hospital of Guangxi Zhuang Autonomous Region, Nanning, ChinaDepartment of Genetic and Metabolic Central Laboratory, Maternal and Child Health Hospital of Guangxi Zhuang Autonomous Region, Nanning, ChinaGuangxi Clinical Research Center for Birth Defects, Guangxi Key Laboratory of Reproductive Health and Birth Defects Prevention, Maternal and Child Health Hospital of Guangxi Zhuang Autonomous Region, Nanning, ChinaDepartment of Genetic and Metabolic Central Laboratory, Maternal and Child Health Hospital of Guangxi Zhuang Autonomous Region, Nanning, ChinaGuangxi Clinical Research Center for Birth Defects, Guangxi Key Laboratory of Reproductive Health and Birth Defects Prevention, Maternal and Child Health Hospital of Guangxi Zhuang Autonomous Region, Nanning, ChinaDepartment of Genetic and Metabolic Central Laboratory, Maternal and Child Health Hospital of Guangxi Zhuang Autonomous Region, Nanning, ChinaDepartment of Child Health Care, Maternal and Child Health Hospital of Guangxi Zhuang Autonomous Region, Nanning, ChinaGuangxi Clinical Research Center for Birth Defects, Guangxi Key Laboratory of Reproductive Health and Birth Defects Prevention, Maternal and Child Health Hospital of Guangxi Zhuang Autonomous Region, Nanning, ChinaDepartment of Genetic and Metabolic Central Laboratory, Maternal and Child Health Hospital of Guangxi Zhuang Autonomous Region, Nanning, ChinaGuangxi Clinical Research Center for Birth Defects, Guangxi Key Laboratory of Reproductive Health and Birth Defects Prevention, Maternal and Child Health Hospital of Guangxi Zhuang Autonomous Region, Nanning, ChinaDepartment of Genetic and Metabolic Central Laboratory, Maternal and Child Health Hospital of Guangxi Zhuang Autonomous Region, Nanning, ChinaGuangxi Clinical Research Center for Birth Defects, Guangxi Key Laboratory of Reproductive Health and Birth Defects Prevention, Maternal and Child Health Hospital of Guangxi Zhuang Autonomous Region, Nanning, ChinaDepartment of Genetic and Metabolic Central Laboratory, Maternal and Child Health Hospital of Guangxi Zhuang Autonomous Region, Nanning, ChinaGuangxi Clinical Research Center for Birth Defects, Guangxi Key Laboratory of Reproductive Health and Birth Defects Prevention, Maternal and Child Health Hospital of Guangxi Zhuang Autonomous Region, Nanning, ChinaDepartment of Genetic and Metabolic Central Laboratory, Maternal and Child Health Hospital of Guangxi Zhuang Autonomous Region, Nanning, ChinaGuangxi Clinical Research Center for Birth Defects, Guangxi Key Laboratory of Reproductive Health and Birth Defects Prevention, Maternal and Child Health Hospital of Guangxi Zhuang Autonomous Region, Nanning, ChinaDepartment of Genetic and Metabolic Central Laboratory, Maternal and Child Health Hospital of Guangxi Zhuang Autonomous Region, Nanning, ChinaGuangxi Clinical Research Center for Birth Defects, Guangxi Key Laboratory of Reproductive Health and Birth Defects Prevention, Maternal and Child Health Hospital of Guangxi Zhuang Autonomous Region, Nanning, ChinaDepartment of Genetic and Metabolic Central Laboratory, Maternal and Child Health Hospital of Guangxi Zhuang Autonomous Region, Nanning, ChinaGuangxi Clinical Research Center for Pediatric Diseases, Maternal and Child Health Hospital of Guangxi Zhuang Autonomous Region, Nanning, ChinaAs a component of the ubiquitin ligase complex, Cullin 4B (CUL4B) is involved in the process of ubiquitination of different substrates, controlling genome stability, nucleotide excision repair, and chromatin-remodeling. The mutations in the CUL4B gene are revealed to be a cause of Cabezas syndrome (OMIM 300354), a rare syndromic form of X-linked intellectual disability (XLID). In this study, whole-exome sequencing analysis and Sanger sequencing identified two maternally inherited likely pathogenetic variants (CUL4B, NM_001079872.2: c.803dupT/p. Leu268fs*5; c.953_957delTTATA/p. Ile318fs*2) in two probands, respectively. Patients carrying CUL4B variants presented with broad and variable phenotypic defects. The clinical manifestations of the two boys are consistent with Cabezas syndrome; however, they exhibit significant heterogeneity compared to previously reported cases. Phenotypic manifestations resulting from genetic variations may exhibit population differences and, in some cases, may present with concealed or latent expressions. Therefore, regular pediatric health check-ups and appropriate molecular diagnostic techniques are essential for the early detection, diagnosis, and treatment of such disorders. Our findings could be used to better define the genetic map in this area and will be valuable in the genetic diagnosis of the disease.https://www.frontiersin.org/articles/10.3389/fnins.2025.1600852/fullCUL4BCabezas syndromeintellectual disabilitydevelopmental delayseizuresnovel variant |
| spellingShingle | Li Lin Li Lin Qi Yang Qi Yang Shujie Zhang Shujie Zhang Xunzhao Zhou Xunzhao Zhou Xiaoling Li Sheng Yi Sheng Yi Qiang Zhang Qiang Zhang Shang Yi Shang Yi Sheng He Sheng He Zailong Qin Zailong Qin Jingsi Luo Jingsi Luo Jingsi Luo Case Report: Cabezas syndrome caused by CUL4B gene mutations in two unrelated Chinese boys Frontiers in Neuroscience CUL4B Cabezas syndrome intellectual disability developmental delay seizures novel variant |
| title | Case Report: Cabezas syndrome caused by CUL4B gene mutations in two unrelated Chinese boys |
| title_full | Case Report: Cabezas syndrome caused by CUL4B gene mutations in two unrelated Chinese boys |
| title_fullStr | Case Report: Cabezas syndrome caused by CUL4B gene mutations in two unrelated Chinese boys |
| title_full_unstemmed | Case Report: Cabezas syndrome caused by CUL4B gene mutations in two unrelated Chinese boys |
| title_short | Case Report: Cabezas syndrome caused by CUL4B gene mutations in two unrelated Chinese boys |
| title_sort | case report cabezas syndrome caused by cul4b gene mutations in two unrelated chinese boys |
| topic | CUL4B Cabezas syndrome intellectual disability developmental delay seizures novel variant |
| url | https://www.frontiersin.org/articles/10.3389/fnins.2025.1600852/full |
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