AUTHOR=Wang Yu , Song Hanqing , Yu Lingling , Wu Nan , Zheng Xiaodong , Liang Bo , Wang Peiguang 

TITLE=A novel mutation in SPINK5 gene underlies a case of atypical Netherton syndrome

JOURNAL=Frontiers in Genetics

VOLUME=Volume 13 - 2022

YEAR=2022

URL=https://www.frontiersin.org/journals/genetics/articles/10.3389/fgene.2022.943264

DOI=10.3389/fgene.2022.943264

ISSN=1664-8021

ABSTRACT=Netherton syndrome (NS, OMIM #256500) is a rare autosomal recessive disease characterized by a triad of congenital ichthyosiform erythroderma (CIE) or ichthyosis linearis circumflexa (ILC), trichorrhexis invaginata (TI), and atopic predisposition. The disease is caused by a mutation in the SPINK5 gene (serine protease inhibitor of kazal type 5) on chromosome 5q32 encoding LEKTI (lymphoepithelial kazal type-related inhibitor). We performed whole exome sequencing on a NS Chinese family and genotype-phenotype correlation analysis in the patients with NS and congenital ichthyosis erythroderma. We identified a novel frameshift mutation c.2474_2475del (p.Glu825Glyfs*2) in the SPINK5 gene. The N-terminal mutations of LEKTI cause a severer phenotype, while the C-terminal mutations of LEKT1 are related to a milder phenotype. Our findings suggest that Netherton syndrome may be underestimated clinically, and further expand the reservoir of SPINK5 mutations in Netherton syndrome.