Genetic spectrum of Chinese children with cystic fibrosis: comprehensive data analysis from the main referral centre in China

被引:4
作者
Shen, Yuelin [1 ]
Tang, Xiaolei [1 ]
Chen, Qionghua [2 ]
Xu, Hui [1 ]
Liu, Hui [1 ]
Liu, Jinrong [1 ]
Yang, Haiming [1 ]
Li, Huimin [1 ]
Zhao, Shunying [1 ]
机构
[1] Capital Med Univ, Beijing Childrens Hosp, Natl Clin Res Ctr Resp Dis, Natl Ctr Childrens Hlth,Dept Resp Med 2, Beijing, Peoples R China
[2] Quanzhou Childrens Hosp, Quanzhou, Peoples R China
基金
中国国家自然科学基金;
关键词
Cystic fibrosis; Genotype; MUTATION; PATIENT; PHENOTYPES; DIAGNOSIS; CONSENSUS; SWEAT;
D O I
10.1136/jmg-2022-108501
中图分类号
Q3 [遗传学];
学科分类号
071007 ; 090102 ;
摘要
Background and objectives 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. Methods 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. Results 158 different variants including 23 novel observations were identified after sequencing. The majority of CFTR 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. Conclusions 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.
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页码:310 / 315
页数:6
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