Whole-Exome Sequencing Identified CFTR Variants in Two Consanguineous Families in China

被引:2
作者
Yang, Binyi [1 ,2 ,3 ]
Lei, Cheng [1 ,2 ,3 ]
Yang, Danhui [1 ,2 ,3 ]
Tan, Zhiping [4 ]
Guo, Ting [1 ,2 ,3 ]
Luo, Hong [1 ,2 ,3 ]
机构
[1] Cent South Univ, Xiangya Hosp 2, Dept Pulm & Crit Care Med, Changsha, Peoples R China
[2] Cent South Univ, Res Unit Resp Dis, Changsha, Peoples R China
[3] Hunan Diag & Treatment Ctr Resp Dis, Changsha, Peoples R China
[4] Cent South Univ, Dept Cardiovasc Surg, Clin Ctr Gene Diag & Therapy, Xiangya Hosp 2, Changsha, Peoples R China
基金
中国国家自然科学基金;
关键词
cystic fibrosis; CFTR; bronchiectasis; Chinese; genetic variants; phenotype; CYSTIC-FIBROSIS; MUTATIONS; GENE; DISEASE; ALLELE;
D O I
10.3389/fgene.2021.631221
中图分类号
Q3 [遗传学];
学科分类号
071007 ; 090102 ;
摘要
Background Cystic fibrosis (CF) is an autosomal recessive disease caused by genetic variants of the cystic fibrosis transmembrane conductance regulator (CFTR) gene. It is a common hereditary disease in Caucasians while rare in the Chinese. Until now, only 87 Chinese patients have been reported with molecular confirmations. The variant spectrum and clinical features of Chinese CF patients are obviously different from those of Caucasians. Materials and Methods Whole-exome sequencing was applied to analyze the exome of three individuals who have only the typical CF phenotype in the respiratory system from two consanguineous families. The protein domain and structure analysis were applied to predict the impact of the variants. Sanger sequencing was applied to validate the candidate variants. Results A previously reported homozygous variant in CFTR (NM_000492.4: c.1000C > T, p.R334W) was identified in proband I. A novel homozygous variant in a polymorphic position (NM_000492.4: c.1409T > A, p.V470E) was identified in two individuals in the family II. The novel CFTR variant predicted to be disease-causing is the first, to the best of our knowledge, to be reported in CFTR. However, in vitro validation is still needed. Conclusion Our finding expands the variant spectrum of CFTR, reveals clearer clinical phenotype distinction and variant spectrum distinction between Chinese and Caucasian CF patients, and contributes to a more rapid genetic diagnosis and future genetic counseling.
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页数:8
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