A Novel SPINK5 Gene Mutation Associated with Netherton Syndrome in an Omani Patient

Abstract

Netherton syndrome (NS) is an autosomal recessive primary immunodeficiency. It is characterised by substantial skin barrier defects and is often misdiagnosed as severe atopic dermatitis or hyper-immunoglobulin E syndrome. Although more than 80 NS-associated pathogenic mutations in the serine peptidase inhibitor kazal type 5 (SPINK5) gene have been reported worldwide, only one has been reported in the Arab population to date. We report the case of a novel association between the c.1887+1G>A mutation in the SPINK5 gene and NS in an Omani-Arab patient born in 2014 who was managed at a paediatric immunology clinic in Muscat, Oman. Accurate genetic diagnosis facilitated tailored clinical management of the index patient and enabled the provision of genetic counselling and offering of future reproductive options to the individuals related to the index patient.

Keywords: Case report; Congenital Ichthyosiform Erythroderma; Genetics; Netherton Syndrome; Oman; Primary Immunodeficiency Disease; Serine Peptidase Inhibitor Kazal Type 5.

Figure 1

Family pedigree of the index patient. A sibling of the index patient (red arrow) was affected and had previously died of sepsis. Two paternal cousins who presented with features similar to the index patient also died of sepsis before the age of one year.

Figure 2

Haemotoxylin and eosin stain of a skin biopsy of the index patient at ×10 magnification showing psoriasiform acanthosis spongiosis, mild lymphocytic exocytosis with occasional dyskeratotic cells.

Figure 3

Outputs showing evidence for pathogenicity of the c.1888+1G>A mutation. A: Family segregation analysis using Sanger sequencing data of the exon 20-intron 20 junction shows the c.1888+1G>A mutation as homozygous in the index patient (asterisk) and as heterozygous (R indicates G/A transition) in the parents of the index patient. The unaffected sibling of the index patient does not carry the mutated allele. B: Results from the in silico analysis using the Human Splicing Finder suite (GENOMNIS) indicates that the c.1888+1G>A mutation probably affects splicing at the exon 20-intron 20 junction.