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

Frontiers in Genetics

Zhiping Tan¹  Cheng Lei³  Binyi Yang³  Danhui Yang³  Hong Luo³  Ting Guo³ 

[1] Department of Cardiovascular Surgery, Clinical Center for Gene Diagnosis and Therapy, The Second Xiangya Hospital of Central South University, Changsha, China;Department of Pulmonary and Critical Care Medicine, The Second Xiangya Hospital, Central South University, Changsha, China;Hunan Diagnosis and Treatment Center of Respiratory Disease, Changsha, China;Research Unit of Respiratory Disease, Central South University, Changsha, China;

关键词: cystic fibrosis;    CFTR;    bronchiectasis;    Chinese;    genetic variants;    phenotype;   

DOI  :  10.3389/fgene.2021.631221

来源: DOAJ

【 摘 要 】

BackgroundCystic 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 MethodsWhole-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.ResultsA 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.ConclusionOur 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.

【 授权许可】

Unknown