Shen Yuelin, Tang Xiaolei, Chen Qionghua, Xu Hui, Liu Hui, Liu Jinrong, Yang Haiming, Li Huimin, Zhao Shunying
Department II of Respiratory Medicine, National Clinical Research Center for Respiratory Diseases, Beijing Children's Hospital, Capital Medical University, National Center for Children's Health, Beijing, People's Republic of China.
Quanzhou Children's Hospital, Quanzhou, People's Republic of China.
J Med Genet. 2022 Jul 20;60(3):310-5. doi: 10.1136/jmg-2022-108501.
Cystic fibrosis (CF) is a heterogeneous disease with a diverse genetic spectrum among populations. Few patients with CF of Chinese origin have been reported worldwide. The objective of this study is to characterise the genotypic features of CF in Chinese children.
We recruited and characterised the genetic manifestations of 103 Chinese children with CF in Beijing Children's Hospital from 2010 to 2022. Whole-exome sequencing were performed to define the genotypes. Meanwhile, other 99 genetically confirmed patients with Chinese origin described in 45 references were also summarised.
158 different variants including 23 novel observations were identified after sequencing. The majority of variants (82.3%) in Chinese have been observed only once or twice. 43.7% of the variants were only identified in patients of Chinese origin. The c.2909G>A(p.Gly970Asp), c.1766+5G>T and c.1657C>T(p.Arg553X) were the most frequent variants among Chinese patients, with allele frequency of 12.1%, 5.4% and 3.6%, respectively. The first two variants both showed significant Chinese ethnic tendency, while the latter one most likely came from Europeans for historical reasons. They also demonstrated significant differences in geographical distribution. c.1521_1523delCTT(p.F508del) was rarely observed in patients of pure Chinese origin, with an allele frequency of 1.8%. Two de novo variants (c.960dupA[p.Ser321IlefsX43] and c.2491-2A>G) and two deep-intronic variants (c.3718-2477C>T and c.3874-4522A>G) were identified, which were also quite rare among Chinese.
The genetic spectrum of CF in Chinese is unique and quite different from that observed in Caucasians. The geographical distributions of the most frequent variants were reported for the first time.
囊性纤维化（CF）是一种异质性疾病，不同人群的遗传谱各不相同。全球范围内报道的华裔CF患者很少。本研究的目的是描述中国儿童CF的基因型特征。
我们招募并分析了2010年至2022年在北京儿童医院就诊的103例中国CF儿童的遗传表现。进行全外显子组测序以确定基因型。同时，还总结了45篇参考文献中描述的另外99例经基因确认的华裔患者。
测序后共鉴定出158种不同变异，其中包括23种新发现。中国患者中大多数变异（82.3%）仅被观察到一两次。43.7%的变异仅在中国患者中被鉴定出。c.2909G>A（p.Gly970Asp）、c.1766+5G>T和c.1657C>T（p.Arg553X）是中国患者中最常见的变异，等位基因频率分别为12.1%、5.4%和3.6%。前两个变异均显示出明显的中国民族倾向，而后者很可能由于历史原因来自欧洲人。它们在地理分布上也表现出显著差异。c.1521_1523delCTT（p.F508del）在纯华裔患者中很少见，等位基因频率为1.8%。鉴定出两个新发变异（c.960dupA[p.Ser321IlefsX43]和c.2491-2A>G）以及两个内含子深处变异（c.3718-2477C>T和c.3874-4522A>G），这些在中国人群中也相当罕见。
中国CF患者的遗传谱是独特的，与白种人观察到的情况有很大不同。首次报道了最常见变异的地理分布情况。
