A large deletion in the CFTR gene in CBAVD

Area of Science:

• Genetics
• Reproductive Medicine
• Molecular Biology

Background:

• Standard cystic fibrosis transmembrane regulator (CFTR) gene mutation screening often misses large exon deletions and duplications.
• Congenital bilateral absence of the vas deferens (CBAVD) is a condition where routine CFTR mutation analysis may be incomplete.

Purpose of the Study:

• To investigate the prevalence of large exon deletions and duplications in the CFTR gene among patients diagnosed with CBAVD.
• To identify CFTR gene mutations in CBAVD patients who had negative or single-mutation results from standard screening.

Main Methods:

• Employed a laboratory-developed semiquantitative fluorescent PCR assay to detect exonic deletions and duplications in the CFTR gene.
• Analyzed DNA samples from 48 men diagnosed with CBAVD.

Main Results:

• A large deletion in exons 22-24 of the CFTR gene was identified in one (2%) of the 48 CBAVD patients.
• This patient was previously known to carry only the IVS8-5T mutation, indicating a missed large deletion.
• A one-base pair insertion in exon 17b, disrupting the reading frame, was found in a second patient with the IVS8-5T mutation.

Conclusions:

• Comprehensive analysis of the CFTR gene, including screening for exon deletions and duplications, is essential for a complete genetic evaluation of CBAVD patients.
• Such thorough genetic testing is particularly important for CBAVD individuals considering assisted reproduction options.