Clinical relevance of loss-of-function mutations of NEMO/IKBKG
Dysfunctional inhibitor of nuclear factor-κB (NF-κB) kinase regulatory subunit gamma (IKBKG) is known to trigger incontinentia pigmenti (IP), anhidrotic ectodermal dysplasia with immunodeficiency (EDA-ID), immunodeficiency (ID), and IKBKG deleted exon 5 autoinflammatory syndrome (NDAS). The correlat...
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KeAi Communications Co., Ltd.
2025-09-01
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| Series: | Genes and Diseases |
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| Online Access: | http://www.sciencedirect.com/science/article/pii/S2352304225000200 |
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| author | Jin Wang Kexin Shen Hongxia Lou Lina Zhou Yunfei An Xiaodong Zhao Yuan Ding |
| author_facet | Jin Wang Kexin Shen Hongxia Lou Lina Zhou Yunfei An Xiaodong Zhao Yuan Ding |
| author_sort | Jin Wang |
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| description | Dysfunctional inhibitor of nuclear factor-κB (NF-κB) kinase regulatory subunit gamma (IKBKG) is known to trigger incontinentia pigmenti (IP), anhidrotic ectodermal dysplasia with immunodeficiency (EDA-ID), immunodeficiency (ID), and IKBKG deleted exon 5 autoinflammatory syndrome (NDAS). The correlation between genotype and phenotype remains elusive because of the considerable variability in IKBKG genes. This study aimed to systematically describe IKBKG gene mutations and clinical characteristics. Cases with IKBKG mutations and thorough clinical features were gathered using PubMed, Web of Science, EMBASE, Scopus, and Cochrane databases, with a publication deadline of February 12, 2023. The Newcastle-Ottawa scale and its modified version were used to assess the quality of each study. Gene mutations and clinical manifestation data were analyzed and reviewed. 144 publications with 564 patients were included in the analysis. IP, EDA-ID, ID, and NDAS accounted for 78.0%, 15.8%, 5.0%, and 1.2% of IKBKG mutations, respectively. Skin abnormalities (89.5%), dental abnormalities (68.5%), infection (100%), and non-infectious inflammation (100%) were the most common manifestations of IP, EDA-ID, ID, and NDAS, respectively. Mutations related to EDA-ID and ID are concentrated in the zinc finger region and characterized by the most severe clinical symptoms. E390RfsX5 can cause IP, EDA-ID, and ID. c.1182_1183delTT and H413R caused the most clinical manifestations. Mycobacterium (22.7%) and Streptococcus (17.5%) were the most common pathogens. Almost all cases of hyper-IgM occurred in patients with EDA-ID. Different structural domains correspond to symptoms with varying degrees of severity. Certain mutations may correspond to unique manifestations, providing insight into disease progression. |
| format | Article |
| id | doaj-art-bbc88f972ec64aef97c2af3189b90e09 |
| institution | DOAJ |
| issn | 2352-3042 |
| language | English |
| publishDate | 2025-09-01 |
| publisher | KeAi Communications Co., Ltd. |
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| series | Genes and Diseases |
| spelling | doaj-art-bbc88f972ec64aef97c2af3189b90e092025-08-20T03:15:02ZengKeAi Communications Co., Ltd.Genes and Diseases2352-30422025-09-0112510153110.1016/j.gendis.2025.101531Clinical relevance of loss-of-function mutations of NEMO/IKBKGJin Wang0Kexin Shen1Hongxia Lou2Lina Zhou3Yunfei An4Xiaodong Zhao5Yuan Ding6Growth, Development and Mental Health Center of Children and Adolescents, Children’s Hospital of Chongqing Medical University, Chongqing Key Laboratory of Child Neurodevelopment and Cognitive Disorders, National Clinical Research Center for Child Health and Disorders, Ministry of Education Key Laboratory of Child Development and Disorders, Chongqing 401146, ChinaGrowth, Development and Mental Health Center of Children and Adolescents, Children’s Hospital of Chongqing Medical University, Chongqing Key Laboratory of Child Neurodevelopment and Cognitive Disorders, National Clinical Research Center for Child Health and Disorders, Ministry of Education Key Laboratory of Child Development and Disorders, Chongqing 401146, ChinaGrowth, Development and Mental Health Center of Children and Adolescents, Children’s Hospital of Chongqing Medical University, Chongqing Key Laboratory of Child Neurodevelopment and Cognitive Disorders, National Clinical Research Center for Child Health and Disorders, Ministry of Education Key Laboratory of Child Development and Disorders, Chongqing 401146, ChinaChongqing Key Laboratory of Child Infection and Immunity, Children's Hospital of Chongqing Medical University, Chongqing 400014, ChinaChongqing Key Laboratory of Child Infection and Immunity, Children's Hospital of Chongqing Medical University, Chongqing 400014, ChinaChongqing Key Laboratory of Child Infection and Immunity, Children's Hospital of Chongqing Medical University, Chongqing 400014, ChinaGrowth, Development and Mental Health Center of Children and Adolescents, Children’s Hospital of Chongqing Medical University, Chongqing Key Laboratory of Child Neurodevelopment and Cognitive Disorders, National Clinical Research Center for Child Health and Disorders, Ministry of Education Key Laboratory of Child Development and Disorders, Chongqing 401146, China; Chongqing Key Laboratory of Child Infection and Immunity, Children's Hospital of Chongqing Medical University, Chongqing 400014, China; Corresponding author. Children's Hospital of Chongqing Medical University, Chongqing 400014, China.Dysfunctional inhibitor of nuclear factor-κB (NF-κB) kinase regulatory subunit gamma (IKBKG) is known to trigger incontinentia pigmenti (IP), anhidrotic ectodermal dysplasia with immunodeficiency (EDA-ID), immunodeficiency (ID), and IKBKG deleted exon 5 autoinflammatory syndrome (NDAS). The correlation between genotype and phenotype remains elusive because of the considerable variability in IKBKG genes. This study aimed to systematically describe IKBKG gene mutations and clinical characteristics. Cases with IKBKG mutations and thorough clinical features were gathered using PubMed, Web of Science, EMBASE, Scopus, and Cochrane databases, with a publication deadline of February 12, 2023. The Newcastle-Ottawa scale and its modified version were used to assess the quality of each study. Gene mutations and clinical manifestation data were analyzed and reviewed. 144 publications with 564 patients were included in the analysis. IP, EDA-ID, ID, and NDAS accounted for 78.0%, 15.8%, 5.0%, and 1.2% of IKBKG mutations, respectively. Skin abnormalities (89.5%), dental abnormalities (68.5%), infection (100%), and non-infectious inflammation (100%) were the most common manifestations of IP, EDA-ID, ID, and NDAS, respectively. Mutations related to EDA-ID and ID are concentrated in the zinc finger region and characterized by the most severe clinical symptoms. E390RfsX5 can cause IP, EDA-ID, and ID. c.1182_1183delTT and H413R caused the most clinical manifestations. Mycobacterium (22.7%) and Streptococcus (17.5%) were the most common pathogens. Almost all cases of hyper-IgM occurred in patients with EDA-ID. Different structural domains correspond to symptoms with varying degrees of severity. Certain mutations may correspond to unique manifestations, providing insight into disease progression.http://www.sciencedirect.com/science/article/pii/S2352304225000200Anhidrotic ectodermal dysplasia with immunodeficiency (EDA-ID)Immunodeficiency (ID)Incontinentia pigmenti (IP)Inhibitor of nuclear factor kappa B kinase regulatory subunit gamma (IKBKG)NEMO deleted exon 5 autoinflammatory syndrome (NDAS)Nuclear factor-κB (NF-κB) essential modulator (NEMO) |
| spellingShingle | Jin Wang Kexin Shen Hongxia Lou Lina Zhou Yunfei An Xiaodong Zhao Yuan Ding Clinical relevance of loss-of-function mutations of NEMO/IKBKG Genes and Diseases Anhidrotic ectodermal dysplasia with immunodeficiency (EDA-ID) Immunodeficiency (ID) Incontinentia pigmenti (IP) Inhibitor of nuclear factor kappa B kinase regulatory subunit gamma (IKBKG) NEMO deleted exon 5 autoinflammatory syndrome (NDAS) Nuclear factor-κB (NF-κB) essential modulator (NEMO) |
| title | Clinical relevance of loss-of-function mutations of NEMO/IKBKG |
| title_full | Clinical relevance of loss-of-function mutations of NEMO/IKBKG |
| title_fullStr | Clinical relevance of loss-of-function mutations of NEMO/IKBKG |
| title_full_unstemmed | Clinical relevance of loss-of-function mutations of NEMO/IKBKG |
| title_short | Clinical relevance of loss-of-function mutations of NEMO/IKBKG |
| title_sort | clinical relevance of loss of function mutations of nemo ikbkg |
| topic | Anhidrotic ectodermal dysplasia with immunodeficiency (EDA-ID) Immunodeficiency (ID) Incontinentia pigmenti (IP) Inhibitor of nuclear factor kappa B kinase regulatory subunit gamma (IKBKG) NEMO deleted exon 5 autoinflammatory syndrome (NDAS) Nuclear factor-κB (NF-κB) essential modulator (NEMO) |
| url | http://www.sciencedirect.com/science/article/pii/S2352304225000200 |
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