1. A novel SPINK5 donor splice site variant in a child with Netherton syndrome
- Author
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Nikolai Paul Pace, S. Aquilina, Judith Fischer, Rijad Merdzanic, Isabella Borg, Dillon Mintoff, Liam Mercieca, Johannes Numrich, and Julia Vornweg
- Subjects
0301 basic medicine ,Male ,LEKTI ,RNA Splicing ,Donor splice site ,030105 genetics & heredity ,Biology ,QH426-470 ,Immunofluorescence ,Clinical Reports ,03 medical and health sciences ,SPINK5 ,medicine ,Genetics ,Pathogenic viruses ,Humans ,Netherton syndrome ,Molecular genetics ,Molecular Biology ,Genetics (clinical) ,Splice donor site pathogenic variant ,Clinical Report ,medicine.diagnostic_test ,Genodermatosis ,medicine.disease ,Molecular biology ,030104 developmental biology ,Phenotype ,Child, Preschool ,Skin biopsy ,Mutation ,biology.protein ,Functional significance ,Serine Peptidase Inhibitor Kazal-Type 5 ,Antibody - Abstract
Background Netherton syndrome (NS) is a genodermatosis caused by loss‐of‐function mutations in SPINK5, resulting in aberrant LEKTI expression. Method Next‐generation sequencing of SPINK5 (NM_001127698.1) was carried out and functional studies were performed by immunofluorescence microscopy of a lesional skin biopsy using anti‐LEKTI antibodies. Results We describe a novel SPINK5 likely pathogenic donor splice site variant (NM_001127698.1:c.2015+5G>A) in a patient with NS and confirm its functional significance by demonstrating complete loss of LEKTI expression in lesional skin by immunofluorescence analysis. Conclusion The 2015+5G>A is a novel, likely pathogenic variant in NS. Herein we review and assimilate documented SPINK5 pathogenic variants and discuss possible genotype–phenotype associations in NS., We present a novel SPINK5, likely pathogenic mutation in a patient with Netherton syndrome of Maltese‐Caucasian ethnicity. We also tabulate the spectrum of documented SPINK5 mutations in this genodermatosis and discuss potential genotype–phenotype associations.
- Published
- 2021