1 Department of Immunology and Institute for Cellular and Molecular Medicine, and.
2 South African Medical Research Council Extramural Unit for Stem Cell Research and Therapy, Faculty of Health Sciences, University of Pretoria, Pretoria, South Africa.
Ann Am Thorac Soc. 2017 Jan;14(1):1-7. doi: 10.1513/AnnalsATS.201606-481FR.
Identifying mutations that cause cystic fibrosis (CF) is important for making an early, unambiguous diagnosis, which, in turn, is linked to better health and a greater life expectancy. In patients of African descent, a molecular diagnosis is often confounded by the fact that the majority of investigations undertaken to identify causative mutations have been conducted on European populations, and CF-causing mutations tend to be population specific. We undertook a survey of published data with the aim of identifying causative CF mutations in patients of African descent in the Americas. We found that 1,584 chromosomes had been tested in only 6 countries, of which 876 alleles (55.3%) still remained unidentified. There were 59 mutations identified. Of those, 41 have been shown to cause CF, 17 have no associated functional studies, and one (R117H) is of varying clinical consequence. The most common mutations identified in the patients of African descent were: ΔF508 (29.4% identified in the United States, Colombia, Brazil, and Venezuela); 3120 + 1G>A (8.4% identified in Brazil, the United States, and Colombia); G85E (3.8% identified in Brazil); 1811 + 1.6kbA>G (3.7% identified in Colombia); and 1342 - 1G>C (3.1% identified in the United States). The majority of the mutations identified (81.4%) have been described in just one country. Our findings indicate that there is a need to fully characterize the spectrum of CF mutations in the diaspora to improve diagnostic accuracy for these patients and facilitate treatment.
确定导致囊性纤维化 (CF) 的突变对于进行早期、明确的诊断很重要，而早期、明确的诊断又与更好的健康状况和更长的预期寿命相关。在非洲裔患者中，由于大多数用于确定致病突变的研究都是在欧洲人群中进行的，而且导致 CF 的突变往往具有人群特异性，因此分子诊断常常变得复杂。我们进行了一项已发表数据的调查，旨在确定美洲非洲裔患者中的致病 CF 突变。我们发现，仅在 6 个国家对 1584 条染色体进行了测试，其中 876 个等位基因（55.3%）仍然无法识别。共确定了 59 个突变。其中，有 41 个已被证实可导致 CF，有 17 个没有相关的功能研究，还有 1 个（R117H）具有不同的临床后果。在非洲裔患者中发现的最常见的突变是：ΔF508（在美国、哥伦比亚、巴西和委内瑞拉，29.4%被识别）；3120 + 1G>A（在巴西、美国和哥伦比亚，8.4%被识别）；G85E（在巴西，3.8%被识别）；1811 + 1.6kbA>G（在哥伦比亚，3.7%被识别）；以及 1342 - 1G>C（在美国，3.1%被识别）。大多数被识别的突变（81.4%）仅在一个国家被描述过。我们的发现表明，需要全面描述散居地中 CF 突变的全貌，以提高这些患者的诊断准确性并促进治疗。
