Novel mutations and polymorphisms in the CFTR gene associated with three subtypes of congenital absence of vas deferens

Detection of mutations in all coding regions of the CFTR gene has great significance for patients with congenital absence of vas deferens, particularly because the relevant studies have not been performed in China.


Xiaojian Yang, M.D., Qipeng Sun, M.D., Ping Yuan, M.D., Ph.D., Hao Liang, Ph.D., Xiao Wu, M.D., Luhua Lai, Ph.D., Yan Zhang, M.D., Ph.D.

Volume 104, Issue 5, Pages 1268-1275



To study the new genotypes in congenital absence of vas deferens (CAVD) and the correlation with different phenotypes, and to investigate the pathogenesis of the disease based on bioinformatics analysis.


Case-control study.


University-affiliated tertiary teaching hospital.


Nineteen patients with CAVD and azoospermia. The time period of the study was from May 2013 to April 2014.



Main Outcome Measure(s):

Sanger sequencing was performed in the coding regions and intron–exon boundaries of the CFTR gene on the polymerase chain reaction (PCR) products. Mutations/variations were identified and compared with the control subjects, and bioinformatics analysis searched in the dbSNP and 1000 Genomes Project. Functional effects of the novel mutations were predicted. Structural modeling of the wild and mutant proteins was also performed.


A total of 8 mutations were identified in 12 patients, 4 of which were novel (c.4433C>G, c.3469-3C>A, c.1357delT, and c.3407C>T). The mutation c.4433C>G occurred in the PDZ-binding motif in the CFTR protein, which was predicted to disrupt the interaction between CFTR and CAL. Another missense mutation, c.3407C>T, was predicted to damage and destroy the transmembrane adenosine triphosphate (ATP)-binding cassette domain. The splicing mutation, c.3469-3C>A, was predicted to truncate exon 22 by Human Splicing Finder. The frameshift mutation, c.1357delT, was predicted to introduce a premature stop codon at position 453 and lead to 1,012 amino acids truncation at the carboxyl terminus of the CFTR protein.


This study illustrates the significance of whole exon sequencing of the CFTR gene in patients with CAVD. It is essential for determining the pathogenesis of novel mutations using bioinformatics analysis and to identify correlation between new genotypes and phenotypes.

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