title: Detection of a large heterozygous deletion and a splicing defect in the CFTR transcripts from nasal swab of a Japanese case of cystic fibrosis.
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.
authors.affiliation: Department of Human Nutrition, Nagoya University Graduate School of Medicine, Research Center of Health, Physical Fitness and Sports, Nagoya University, Nagoya, Japan.
authors.forename: Miyuki
authors.initials: M
authors.lastname: Nakakuki
authors.forename: Kotoyo
authors.initials: K
authors.lastname: Fujiki
authors.forename: Akiko
authors.initials: A
authors.lastname: Yamamoto
authors.forename: Shigeru B H
authors.initials: SB
authors.lastname: Ko
authors.forename: Lanjuan
authors.initials: L
authors.lastname: Yi
authors.forename: Mariko
authors.initials: M
authors.lastname: Ishiguro
authors.forename: Makoto
authors.initials: M
authors.lastname: Yamaguchi
authors.forename: Shiho
authors.initials: S
authors.lastname: Kondo
authors.forename: Shinsuke
authors.initials: S
authors.lastname: Maruyama
authors.forename: Kosuke
authors.initials: K
authors.lastname: Yanagimoto
authors.forename: Satoru
authors.initials: S
authors.lastname: Naruse
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Ishiguro
mesh_terms: D000483:Alleles; D044466:Asian People; D001483:Base Sequence; D002712:Chlorides / Q000032:analysis / Q000378:metabolism; D003001:Cloning, Molecular; D003550:Cystic Fibrosis / Q000175:diagnosis / Q000235:genetics*; D019005:Cystic Fibrosis Transmembrane Conductance Regulator / Q000235:genetics / Q000378:metabolism*; D005091:Exons; D005820:Genetic Testing / Q000379:methods; D006579:Heterozygote; D006801:Humans; D007223:Infant; D008297:Male; D009297:Nasal Mucosa / Q000378:metabolism; D011401:Promoter Regions, Genetic; D012326:RNA Splicing; D012333:RNA, Messenger / Q000032:analysis / Q000378:metabolism; D017384:Sequence Deletion; D013542:Sweat / Q000378:metabolism
chemical_list: C505032:CFTR protein, human; D002712:Chlorides; D012333:RNA, Messenger; D019005:Cystic Fibrosis Transmembrane Conductance Regulator