Department of Human Nutrition, Nagoya University Graduate School of Medicine, Research Center of Health, Physical Fitness and Sports, Nagoya University, Nagoya, Japan.
J Hum Genet. 2012 Jul;57(7):427-33. doi: 10.1038/jhg.2012.46. Epub 2012 May 10.
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.
囊性纤维化（CF）是一种常染色体隐性疾病，由 CFTR（囊性纤维化跨膜电导调节因子）基因突变引起。尽管 CF 是白种人群体中最常见的遗传性疾病，但在亚洲人群中却很少见。在日本 CF 患者中，很少发现白种人群中常见的 CFTR 致病突变。在本研究中，除了对 CFTR 基因的所有外显子、其边界和启动子区域进行常规 PCR 和直接测序外，还分析了来自鼻拭子的 CFTR 转录本。该男孩因慢性呼吸道感染和汗液氯化物水平升高而被诊断为 CF。通过常规分析未发现 CFTR 的任何致病突变。CFTR 转录本的克隆和序列显示出跨越外显子 16、17a 和 17b 的杂合性缺失。通过多重连接依赖性探针扩增和通过引物行走从基因组 DNA 获得的接头片段的直接序列证实了该缺失，该缺失揭示了突变 c.2908+1085_3367+260del7201。我们还发现了一个剪接缺陷：另一个等位基因的 CFTR 转录本中外显子 1 的缺失/跳过。建议对日本人群 CF 的遗传分析进行鼻拭子 CFTR 转录本分析。
