Analysis of all 34 exons of the SPINK5 gene in Japanese atopic dermatitis patients

Shin Morizane, Mamoru Oouchida, Ko Sunagawa, Saeko Sugimoto, Mina Kobashi, Satoru Sugihara, Hayato Nomura, Kazuhide Tsuji, Atsushi Sato, Yoshihiro Miura, Hiroaki Hattori, Kotaro Tada, Wook Kang Huh, Akemi Seno, Keiji Iwatsuki

Research output: Contribution to journalArticle

2 Citations (Scopus)

Abstract

Lympho-epithelial Kazal-type-related inhibitor (LEKTI) is a large multidomain serine protease inhibitor that is expressed in epidermal keratinocytes. Nonsense mutations of the SPINK5 gene, which codes for LEKTI, cause Netherton syndrome, which is characterized by hair abnormality, ichthyosis, and atopy. A single nucleotide polymorphism (SNP) of SPINK5, p. K420E, is reported to be associated with the pathogenesis of atopic dermatitis (AD). We studied all 34 exons of the SPINK5 gene in Japanese 57 AD patients and 50 normal healthy controls. We detected nine nonsynonymous variants, including p. K420E; these variants had already been registered in the SNP database. Among them, p. R654H (n=1) was found as a heterozygous mutation in the AD patients, but not in the control. No new mutation was detected. We next compared the data of the AD patients with data from the Human Genetic Variation Database provided by Kyoto University; a significant difference was found in the frequency of the p. S368N genotype distribution. PolyPhen-2 and SIFT, two algorithms for predicting the functional effects of amino acid substitutions, showed significant scores for p. R654H. Therefore, R654H might be a risk factor for epidermal barrier dysfunction in some Japanese AD patients.

Original languageEnglish
Pages (from-to)275-282
Number of pages8
JournalActa Medica Okayama
Volume72
Issue number3
Publication statusPublished - Jan 1 2018

Fingerprint

Atopic Dermatitis
Exons
Genes
Polymorphism
Single Nucleotide Polymorphism
Netherton Syndrome
Nucleotides
Genetic Databases
Ichthyosis
Mutation
Serine Proteinase Inhibitors
Nonsense Codon
Medical Genetics
Amino Acid Substitution
Keratinocytes
Hair
Substitution reactions
Genotype
Databases
Amino Acids

Keywords

  • Atopic dermatitis
  • Epidermal barrier dysfunction
  • LEKTI
  • Serine protease inhibitor
  • SPINK5

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)

Cite this

Morizane, S., Oouchida, M., Sunagawa, K., Sugimoto, S., Kobashi, M., Sugihara, S., ... Iwatsuki, K. (2018). Analysis of all 34 exons of the SPINK5 gene in Japanese atopic dermatitis patients. Acta Medica Okayama, 72(3), 275-282.

Analysis of all 34 exons of the SPINK5 gene in Japanese atopic dermatitis patients. / Morizane, Shin; Oouchida, Mamoru; Sunagawa, Ko; Sugimoto, Saeko; Kobashi, Mina; Sugihara, Satoru; Nomura, Hayato; Tsuji, Kazuhide; Sato, Atsushi; Miura, Yoshihiro; Hattori, Hiroaki; Tada, Kotaro; Huh, Wook Kang; Seno, Akemi; Iwatsuki, Keiji.

In: Acta Medica Okayama, Vol. 72, No. 3, 01.01.2018, p. 275-282.

Research output: Contribution to journalArticle

Morizane, S, Oouchida, M, Sunagawa, K, Sugimoto, S, Kobashi, M, Sugihara, S, Nomura, H, Tsuji, K, Sato, A, Miura, Y, Hattori, H, Tada, K, Huh, WK, Seno, A & Iwatsuki, K 2018, 'Analysis of all 34 exons of the SPINK5 gene in Japanese atopic dermatitis patients', Acta Medica Okayama, vol. 72, no. 3, pp. 275-282.
Morizane S, Oouchida M, Sunagawa K, Sugimoto S, Kobashi M, Sugihara S et al. Analysis of all 34 exons of the SPINK5 gene in Japanese atopic dermatitis patients. Acta Medica Okayama. 2018 Jan 1;72(3):275-282.
Morizane, Shin ; Oouchida, Mamoru ; Sunagawa, Ko ; Sugimoto, Saeko ; Kobashi, Mina ; Sugihara, Satoru ; Nomura, Hayato ; Tsuji, Kazuhide ; Sato, Atsushi ; Miura, Yoshihiro ; Hattori, Hiroaki ; Tada, Kotaro ; Huh, Wook Kang ; Seno, Akemi ; Iwatsuki, Keiji. / Analysis of all 34 exons of the SPINK5 gene in Japanese atopic dermatitis patients. In: Acta Medica Okayama. 2018 ; Vol. 72, No. 3. pp. 275-282.
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abstract = "Lympho-epithelial Kazal-type-related inhibitor (LEKTI) is a large multidomain serine protease inhibitor that is expressed in epidermal keratinocytes. Nonsense mutations of the SPINK5 gene, which codes for LEKTI, cause Netherton syndrome, which is characterized by hair abnormality, ichthyosis, and atopy. A single nucleotide polymorphism (SNP) of SPINK5, p. K420E, is reported to be associated with the pathogenesis of atopic dermatitis (AD). We studied all 34 exons of the SPINK5 gene in Japanese 57 AD patients and 50 normal healthy controls. We detected nine nonsynonymous variants, including p. K420E; these variants had already been registered in the SNP database. Among them, p. R654H (n=1) was found as a heterozygous mutation in the AD patients, but not in the control. No new mutation was detected. We next compared the data of the AD patients with data from the Human Genetic Variation Database provided by Kyoto University; a significant difference was found in the frequency of the p. S368N genotype distribution. PolyPhen-2 and SIFT, two algorithms for predicting the functional effects of amino acid substitutions, showed significant scores for p. R654H. Therefore, R654H might be a risk factor for epidermal barrier dysfunction in some Japanese AD patients.",
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