Detection of a large heterozygous deletion and a splicing defect in the CFTR transcripts from nasal swab of a Japanese case of cystic fibrosis

Miyuki Nakakuki, Kotoyo Fujiki, Akiko Yamamoto, Shigeru Bh Ko, Lanjuan Yi, Mariko Ishiguro, Makoto Yamaguchi, Shiho Kondo, Shinsuke Maruyama, Kosuke Yanagimoto, Satoru Naruse, Hiroshi Ishiguro

Research output: Contribution to journalArticle

7 Citations (Scopus)

Abstract

Cystic fibrosis (CF) is an autosomal recessive disease caused by mutations in CFTR (CF transmembrane conductance regulator). Although CF is the most common hereditary disease in Caucasians, it is rare in Asian populations. Common disease-causing mutations of CFTR in Caucasians are rarely identified in Japanese patients with CF. In the present study, CFTR transcripts from nasal swab were analyzed in a Japanese boy, in addition to conventional PCR and direct sequence of all exons, their boundaries and promoter region of the CFTR gene. The boy was diagnosed with CF by chronic respiratory infection and the elevated sweat chloride level. None of the disease-causing mutations of CFTR was detected by the conventional analysis. Cloning and sequence of the CFTR transcripts revealed a heterozygous deletion spanning exons 16, 17a and 17b. The deletion was confirmed by multiplex ligation-dependent probe amplification and the direct sequence of the junction fragment obtained from the genomic DNA by primer walking, which revealed the mutation c.2908+1085-3367+260del7201. We also identified a splicing defect: deletion/skipping of exon 1 in the CFTR transcript from the other allele. The analysis of CFTR transcripts from nasal swab is recommended in the genetic analysis of CF in Japanese.

Original languageEnglish
Pages (from-to)427-433
Number of pages7
JournalJournal of Human Genetics
Volume57
Issue number7
DOIs
Publication statusPublished - 2012 Jul

Keywords

  • CFTR
  • Japanese
  • cystic fibrosis
  • large genomic deletion
  • nasal epithelial cells
  • splicing defect
  • transcript analysis

ASJC Scopus subject areas

  • Genetics
  • Genetics(clinical)

Fingerprint Dive into the research topics of 'Detection of a large heterozygous deletion and a splicing defect in the CFTR transcripts from nasal swab of a Japanese case of cystic fibrosis'. Together they form a unique fingerprint.

  • Cite this

    Nakakuki, M., Fujiki, K., Yamamoto, A., Ko, S. B., Yi, L., Ishiguro, M., Yamaguchi, M., Kondo, S., Maruyama, S., Yanagimoto, K., Naruse, S., & Ishiguro, H. (2012). Detection of a large heterozygous deletion and a splicing defect in the CFTR transcripts from nasal swab of a Japanese case of cystic fibrosis. Journal of Human Genetics, 57(7), 427-433. https://doi.org/10.1038/jhg.2012.46