Netherton syndrome: mutation analysis of two Taiwanese families.
Netherton syndrome (NS) is a severe autosomal recessive skin disorder characterized by congenital ichthyosiform erythroderma, hair shaft abnormalities, 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 type of serine protease inhibitor involved in the regulation of skin barrier formation and immunity. In the present report, we describe the mutation analysis of two Taiwanese patients with NS. Patient 1 has heterozygous mutations; the maternal allele has novel T808I (C-T transition in codon 808) and the paternal allele has recurrent R790X (C-T transition in codon 790). Patient 2 is homozygous for a novel polymorphism R267Q (G-A transition in codon 267). The change was not detected in the patient's father. Haplotype analysis revealed that the patient was homozygous for the 5 single nucleotide polymorphisms in the genomic sequence of SPINK5 as well as the flanking (GT)(17) and D5S413, in addition to the discrepancy of R267Q. Nevertheless real-time quantitative PCR analysis revealed no microdeletion in the genomic sequence of SPINK5. Thus uniparental disomy of maternal SPINK5 allele was indicated.
Lin
Shuan-Pei
SP
Division of Genetics and Metabolism, Departments of Pediatrics and Medical Research, Mackay Memorial Hospital, Taipei, Taiwan.
Huang
Shu-Yi
SY
Tu
Mei-Eng
ME
Wu
Yu-Hung
YH
Lin
Cheng-Yueh
CY
Lin
Hsiang-Yu
HY
Lee-Chen
Guey-Jen
GJ
D002648:Child; D002675:Child, Preschool; D018389:Codon, Nonsense / Q000235:genetics; D004247:DNA / Q000235:genetics; D004252:DNA Mutational Analysis / Q000379:methods; D005260:Female; D050172:Genes, X-Linked; D020022:Genetic Predisposition to Disease / Q000208:ethnology / Q000235:genetics*; D006197:Hair / Q000002:abnormalities*; D006239:Haplotypes; D006801:Humans; D006969:Hypersensitivity, Immediate / Q000208:ethnology / Q000235:genetics; D016113:Ichthyosiform Erythroderma, Congenital / Q000208:ethnology / Q000235:genetics*; D020125:Mutation, Missense / Q000235:genetics; D020641:Polymorphism, Single Nucleotide / Q000235:genetics; D053491:Proteinase Inhibitory Proteins, Secretory / Q000235:genetics*; D000074163:Serine Peptidase Inhibitor Kazal-Type 5; D013577:Syndrome; D013624:Taiwan
D018389:Codon, Nonsense; D053491:Proteinase Inhibitory Proteins, Secretory; C120650:SPINK5 protein, human; D000074163:Serine Peptidase Inhibitor Kazal-Type 5; D004247:DNA