The role of SPINK5 mutation distribution in phenotypes of Netherton syndrome
ObjectiveNetherton syndrome (NS) is a rare hereditary dermatosis, and the correlation between genotype and phenotype in this disease warrants further investigation. This study aimed to explore the genotype-phenotype correlation in NS.MethodsWe collect cases from our clinic and relevant literature. A...
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Frontiers Media S.A.
2025-01-01
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| Series: | Frontiers in Genetics |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fgene.2025.1475054/full |
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| author | Min Xu Yujie Shi Li Lin Liang Wang Xianzhong Zhu Jinglin Xiong Jiawen Yin Qing Qi Wenlin Yang |
| author_facet | Min Xu Yujie Shi Li Lin Liang Wang Xianzhong Zhu Jinglin Xiong Jiawen Yin Qing Qi Wenlin Yang |
| author_sort | Min Xu |
| collection | DOAJ |
| description | ObjectiveNetherton syndrome (NS) is a rare hereditary dermatosis, and the correlation between genotype and phenotype in this disease warrants further investigation. This study aimed to explore the genotype-phenotype correlation in NS.MethodsWe collect cases from our clinic and relevant literature. After rigorous screening, we included 162 patients with NS-associated symptoms and SPINK5 mutations. We characterized the distribution and mutation types of allele variants. Logistic regression was employed to analyze the correlation between the location of these variants and phenotypes. Additionally, the association between the homozygous condition of variants and death during infancy was analyzed using the Chi-square test.ResultsAmong 162 patients, we identified 324 allele variants, comprising 75 different mutations. Of these, 73 patients carried heterozygous variants, while 89 patients had homozygous variants. We observed that patients with variants or homozygous variants located in the 5′ half of the gene were more likely to experience failure to thrive (P < 0.05). Similarly, variants or homozygous variants located outside DomainR-5 were also associated with an increased risk of failure to thrive (P < 0.05). Furthermore, variants in domain regions were significantly correlated with the presence of ichthyosis linearis circumflexa (P < 0.01). Patients with homozygous fatal variants (c.153delT, c.1431-12G>A, c.1111C>T, c. 1887 + 1G>A, and c. 995delT) had a higher likelihood of mortality during infancy (P < 0.001).ConclusionOur study provides valuable insights into the genotype-phenotype correlation in Netherton syndrome, enhancing our understanding of the disease and potentially informing the development of future therapeutic approaches. |
| format | Article |
| id | doaj-art-c8d8a0c3534c4fe4ab8f83bf239f7c76 |
| institution | Kabale University |
| issn | 1664-8021 |
| language | English |
| publishDate | 2025-01-01 |
| publisher | Frontiers Media S.A. |
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| series | Frontiers in Genetics |
| spelling | doaj-art-c8d8a0c3534c4fe4ab8f83bf239f7c762025-01-27T06:40:28ZengFrontiers Media S.A.Frontiers in Genetics1664-80212025-01-011610.3389/fgene.2025.14750541475054The role of SPINK5 mutation distribution in phenotypes of Netherton syndromeMin Xu0Yujie Shi1Li Lin2Liang Wang3Xianzhong Zhu4Jinglin Xiong5Jiawen Yin6Qing Qi7Wenlin Yang8Department of Dermatology, The Second Affiliated Hospital of Guangzhou Medical University, Guangzhou, ChinaDepartment of Dermatology, The Second Affiliated Hospital of Guangzhou Medical University, Guangzhou, ChinaDepartment of Dermatology, The Second Affiliated Hospital of Guangzhou Medical University, Guangzhou, ChinaDepartment of Neurology, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, ChinaDepartment of Dermatology, The Second Affiliated Hospital of Guangzhou Medical University, Guangzhou, ChinaDepartment of Dermatology, The Second Affiliated Hospital of Guangzhou Medical University, Guangzhou, ChinaDepartment of Dermatology, The Second Affiliated Hospital of Guangzhou Medical University, Guangzhou, ChinaDepartment of Dermatology, The Second Affiliated Hospital of Guangzhou Medical University, Guangzhou, ChinaDepartment of Dermatology, The Second Affiliated Hospital of Guangzhou Medical University, Guangzhou, ChinaObjectiveNetherton syndrome (NS) is a rare hereditary dermatosis, and the correlation between genotype and phenotype in this disease warrants further investigation. This study aimed to explore the genotype-phenotype correlation in NS.MethodsWe collect cases from our clinic and relevant literature. After rigorous screening, we included 162 patients with NS-associated symptoms and SPINK5 mutations. We characterized the distribution and mutation types of allele variants. Logistic regression was employed to analyze the correlation between the location of these variants and phenotypes. Additionally, the association between the homozygous condition of variants and death during infancy was analyzed using the Chi-square test.ResultsAmong 162 patients, we identified 324 allele variants, comprising 75 different mutations. Of these, 73 patients carried heterozygous variants, while 89 patients had homozygous variants. We observed that patients with variants or homozygous variants located in the 5′ half of the gene were more likely to experience failure to thrive (P < 0.05). Similarly, variants or homozygous variants located outside DomainR-5 were also associated with an increased risk of failure to thrive (P < 0.05). Furthermore, variants in domain regions were significantly correlated with the presence of ichthyosis linearis circumflexa (P < 0.01). Patients with homozygous fatal variants (c.153delT, c.1431-12G>A, c.1111C>T, c. 1887 + 1G>A, and c. 995delT) had a higher likelihood of mortality during infancy (P < 0.001).ConclusionOur study provides valuable insights into the genotype-phenotype correlation in Netherton syndrome, enhancing our understanding of the disease and potentially informing the development of future therapeutic approaches.https://www.frontiersin.org/articles/10.3389/fgene.2025.1475054/fullNetherton syndromeSPINK5genotype-phenotype correlationLEKTIdomain |
| spellingShingle | Min Xu Yujie Shi Li Lin Liang Wang Xianzhong Zhu Jinglin Xiong Jiawen Yin Qing Qi Wenlin Yang The role of SPINK5 mutation distribution in phenotypes of Netherton syndrome Frontiers in Genetics Netherton syndrome SPINK5 genotype-phenotype correlation LEKTI domain |
| title | The role of SPINK5 mutation distribution in phenotypes of Netherton syndrome |
| title_full | The role of SPINK5 mutation distribution in phenotypes of Netherton syndrome |
| title_fullStr | The role of SPINK5 mutation distribution in phenotypes of Netherton syndrome |
| title_full_unstemmed | The role of SPINK5 mutation distribution in phenotypes of Netherton syndrome |
| title_short | The role of SPINK5 mutation distribution in phenotypes of Netherton syndrome |
| title_sort | role of spink5 mutation distribution in phenotypes of netherton syndrome |
| topic | Netherton syndrome SPINK5 genotype-phenotype correlation LEKTI domain |
| url | https://www.frontiersin.org/articles/10.3389/fgene.2025.1475054/full |
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