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A novel SPINK5 donor splice site variant in a child with Netherton syndrome.

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.

SUBMITTER: Mintoff D

PROVIDER: S-EPMC8104165 | biostudies-literature | 2021 Mar

REPOSITORIES: biostudies-literature

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A novel SPINK5 donor splice site variant in a child with Netherton syndrome.

Mintoff Dillon D Borg Isabella I Vornweg Julia J Mercieca Liam L Merdzanic Rijad R Numrich Johannes J Aquilina Susan S Pace Nikolai Paul NP Fischer Judith J

Molecular genetics & genomic medicine 20210203 3

<h4>Background</h4>Netherton syndrome (NS) is a genodermatosis caused by loss-of-function mutations in SPINK5, resulting in aberrant LEKTI expression.<h4>Method</h4>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.<h4>Results</h4>We describe a novel SPINK5 likely pathogenic donor splice site variant (NM_001127698.1:c.2015+5G>A) in a patient with NS and ...[more]

PMID: 33534181

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