Is c.1431-12G>A A common European mutation of SPINK5? report of a patient with Netherton Syndrome

Abstract

Netherton Syndrome (NS) is a very rare genetic skin disease resulting from defects in the SPINK5 gene (encoding the protease inhibitor lympho-epithelial Kazal type inhibitor 1, LEKTI1). In this report, we provide a detailed clinical description of a Polish patient with two SPINK5 mutations, the novel c.1816_1820+21delinsCT and possibly recurrent c.1431-12G>A. A detailed pathogenesis of Netherton Syndrome, on the basis of literature review, is discussed in the view of current knowledge about the LEKT1 molecular processing and activity.

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

“…The latter may potentially result in lethal forms of the disease (Diociaiuti et al, 2013; Itoh et al, 2015). Similarly, a NS patient demonstrating heterozygosity for the SPINK5 variants c.1431‐12G>A and c.1816_1820+21delinsCT was described as having a severe clinical phenotype (erythroderma, hypotonia, hypernatremia, sepsis, and respiratory failure) (Śmigiel et al, 2016), while three patients (born to consanguineous parents) who were homozygous for the c.1431‐12G>A SPINK5 variant exhibited a lethal form of disease (Capri et al, 2011). It is important to note that these inferences are non‐dogmatic, especially since NS patients, who are homozygous for more upstream nonsense mutations than the aforementioned (such as c.997C>T), exhibit a milder, non‐lethal form of NS (Fong et al, 2011).…”

A new splice-site mutation of SPINK5 gene in the Netherton syndrome with different clinical features: A case report

“…As a result, atopic manifestation or disorders (such as atopic dermatitis, asthma, allerjic rhinitis, urticaria, food allergies and increased serum IgE levels) will occur. As a matter of fact, it has been suggested that two-thirds of patients have allergic disorders [ 14 , 15 ]. Our patient had a high serum IgE level but did not have any atopic manifestation or food allergy.…”