A compound heterozygous mutation of the SPINK5 gene in a Taiwanese boy with Netherton syndrome.
Netherton syndrome (NS) is a severe, autosomal, recessive ichthyosis. It is characterized by congenital ichthyosiform erythroderma (CIE), trichorrhexis invaginata (TI) - a distinctive hair-shaft anomaly, and atopic diathesis. Recently, pathogenic mutations were identified in serine protease inhibitor Kazal-type 5 (SPINK5), the gene that encodes lympho-epithelial Kazal-type-related inhibitor (LEKTI), a recently identified type of serine protease inhibitor involved in the regulation of skin barrier formation and immunity. Here we report the mutation analysis of a 7-year-old Taiwanese boy with NS manifesting CIE with pathognomic ichthyosis linearis circumflexa and TI. Direct DNA sequencing of SPINK5 demonstrated a compound heterozygous mutation in the proband, 2260A>T (K754X) in exon 24 and 2468delA in exon 26. The former is a novel mutation and was detected in the mother. The latter mutation was detected in the father and has been previously reported in several European families. Both mutations are expected to result in premature termination codons. Mutation analysis could provide a reliable prenatal diagnosis of this lethal ichthyosis.
Chao
Sheau-Chiou
SC
Department of Dermatology, National Cheng Kung University Hospital, Tainan, Taiwan.
Tsai
Ya-Ming
YM
Lee
Julia Yu-Yun
JY
D002352:Carrier Proteins; D002648:Child; D000013:Congenital Abnormalities / Q000235:genetics; D004252:DNA Mutational Analysis; D006197:Hair / Q000002:abnormalities*; D006801:Humans; D006967:Hypersensitivity / Q000235:genetics; D016113:Ichthyosiform Erythroderma, Congenital / Q000235:genetics*; D008297:Male; D009154:Mutation / Q000235:genetics*; D016133:Polymerase Chain Reaction; D053491:Proteinase Inhibitory Proteins, Secretory; D017422:Sequence Analysis, DNA; D000074163:Serine Peptidase Inhibitor Kazal-Type 5; D015842:Serine Proteinase Inhibitors / Q000235:genetics*; D013577:Syndrome
D002352:Carrier Proteins; D053491:Proteinase Inhibitory Proteins, Secretory; C120650:SPINK5 protein, human; D000074163:Serine Peptidase Inhibitor Kazal-Type 5; D015842:Serine Proteinase Inhibitors