Uncovering incontinentia pigmenti: From DNA sequence to pathophysiology
Incontinentia pigmenti (IP) is an X-linked dominant genodermatosis. The disease is known to be caused by recurrent deletion of exons 4–10 of the Inhibitor Of Nuclear Factor Kappa B Kinase Regulatory Subunit Gamma (IKBKG) gene located at the Xq28 chromosomal region, which encodes for NEMO/IKKgamma, a...
| Main Authors: | , , , , , |
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| Format: | Article |
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Frontiers Research Foundation
2022
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| Online Access: | http://psasir.upm.edu.my/id/eprint/102528/ |
| _version_ | 1848863820378800128 |
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| author | Kang, Nien How Jing, Hazel Yi Leong Dwi Pramono, Zacharias Aloysius Kin, Fon Leong Zee, Wei Lai Wei, Hsum Yap |
| author_facet | Kang, Nien How Jing, Hazel Yi Leong Dwi Pramono, Zacharias Aloysius Kin, Fon Leong Zee, Wei Lai Wei, Hsum Yap |
| author_sort | Kang, Nien How |
| building | UPM Institutional Repository |
| collection | Online Access |
| description | Incontinentia pigmenti (IP) is an X-linked dominant genodermatosis. The disease is known to be caused by recurrent deletion of exons 4–10 of the Inhibitor Of Nuclear Factor Kappa B Kinase Regulatory Subunit Gamma (IKBKG) gene located at the Xq28 chromosomal region, which encodes for NEMO/IKKgamma, a regulatory protein involved in the nuclear factor kappa B (NF-κB) signaling pathway. NF-κB plays a prominent role in the modulation of cellular proliferation, apoptosis, and inflammation. IKBKG mutation that results in a loss-of-function or dysregulated NF-κB pathway contributes to the pathophysiology of IP. Aside from typical skin characteristics such as blistering rash and wart-like skin growth presented in IP patients, other clinical manifestations like central nervous system (CNS) and ocular anomalies have also been detected. To date, the clinical genotype-phenotype correlation remains unclear due to its highly variable phenotypic expressivity. Thus, genetic findings remain an essential tool in diagnosing IP, and understanding its genetic profile allows a greater possibility for personalized treatment. IP is slowly and gradually gaining attention in research, but there is much that remains to be understood. This review highlights the progress that has been made in IP including the different types of mutations detected in various populations, current diagnostic strategies, IKBKG pathophysiology, genotype-phenotype correlation, and treatment strategies, which provide insights into understanding this rare mendelian disorder. |
| first_indexed | 2025-11-15T13:38:59Z |
| format | Article |
| id | upm-102528 |
| institution | Universiti Putra Malaysia |
| institution_category | Local University |
| last_indexed | 2025-11-15T13:38:59Z |
| publishDate | 2022 |
| publisher | Frontiers Research Foundation |
| recordtype | eprints |
| repository_type | Digital Repository |
| spelling | upm-1025282024-03-14T04:30:49Z http://psasir.upm.edu.my/id/eprint/102528/ Uncovering incontinentia pigmenti: From DNA sequence to pathophysiology Kang, Nien How Jing, Hazel Yi Leong Dwi Pramono, Zacharias Aloysius Kin, Fon Leong Zee, Wei Lai Wei, Hsum Yap Incontinentia pigmenti (IP) is an X-linked dominant genodermatosis. The disease is known to be caused by recurrent deletion of exons 4–10 of the Inhibitor Of Nuclear Factor Kappa B Kinase Regulatory Subunit Gamma (IKBKG) gene located at the Xq28 chromosomal region, which encodes for NEMO/IKKgamma, a regulatory protein involved in the nuclear factor kappa B (NF-κB) signaling pathway. NF-κB plays a prominent role in the modulation of cellular proliferation, apoptosis, and inflammation. IKBKG mutation that results in a loss-of-function or dysregulated NF-κB pathway contributes to the pathophysiology of IP. Aside from typical skin characteristics such as blistering rash and wart-like skin growth presented in IP patients, other clinical manifestations like central nervous system (CNS) and ocular anomalies have also been detected. To date, the clinical genotype-phenotype correlation remains unclear due to its highly variable phenotypic expressivity. Thus, genetic findings remain an essential tool in diagnosing IP, and understanding its genetic profile allows a greater possibility for personalized treatment. IP is slowly and gradually gaining attention in research, but there is much that remains to be understood. This review highlights the progress that has been made in IP including the different types of mutations detected in various populations, current diagnostic strategies, IKBKG pathophysiology, genotype-phenotype correlation, and treatment strategies, which provide insights into understanding this rare mendelian disorder. Frontiers Research Foundation 2022-09 Article PeerReviewed Kang, Nien How and Jing, Hazel Yi Leong and Dwi Pramono, Zacharias Aloysius and Kin, Fon Leong and Zee, Wei Lai and Wei, Hsum Yap (2022) Uncovering incontinentia pigmenti: From DNA sequence to pathophysiology. Frontiers in Pediatrics, 10. 01-9. ISSN 2296-2360 https://www.frontiersin.org/articles/10.3389/fped.2022.900606/full 10.3389/fped.2022.900606 |
| spellingShingle | Kang, Nien How Jing, Hazel Yi Leong Dwi Pramono, Zacharias Aloysius Kin, Fon Leong Zee, Wei Lai Wei, Hsum Yap Uncovering incontinentia pigmenti: From DNA sequence to pathophysiology |
| title | Uncovering incontinentia pigmenti: From DNA sequence to pathophysiology |
| title_full | Uncovering incontinentia pigmenti: From DNA sequence to pathophysiology |
| title_fullStr | Uncovering incontinentia pigmenti: From DNA sequence to pathophysiology |
| title_full_unstemmed | Uncovering incontinentia pigmenti: From DNA sequence to pathophysiology |
| title_short | Uncovering incontinentia pigmenti: From DNA sequence to pathophysiology |
| title_sort | uncovering incontinentia pigmenti: from dna sequence to pathophysiology |
| url | http://psasir.upm.edu.my/id/eprint/102528/ http://psasir.upm.edu.my/id/eprint/102528/ http://psasir.upm.edu.my/id/eprint/102528/ |