Whole exome sequencing identifies rare cftr variant in two brothers with cbavd and cuavd

Abstract Introduction Congenital Bilateral Absence of the Vas Deferens (CBAVD) is a condition leading to obstructive azoospermia and male infertility. CBAVD is associated with mutations in the cystic fibrosis transmembrane conductance regulator (CFTR) gene. Congenital Unilateral Absence of the Vas Deferens (CUAVD), where only one vas deferens is missing, is also associated with mutations in the CFTR gene. However, the genetic causes of both conditions are not fully understood and warrant further investigation. We present two brothers, one with CBAVD and one with CUAVD, who were subjected to whole exome sequencing. Objective To assess genetic similarities using whole exome sequencing between two brothers with differing reproductive capacities. Methods Whole exome sequencing was performed in two brothers. Subject A was 39-year-old-male who had previously fathered a child and was diagnosed with CUAVD during his vasectomy. Subject B was a 37-year-old male diagnosed with CBAVD, and genetic testing significant for one copy of a mutated cystic fibrosis gene (unaffected CF carrier). Whole blood was collected. DNA was extracted and quality assessed. Finally, whole exome sequencing was completed. Results Whole exome sequencing results were subjected to annotation and filtering. Both subjects were noted to share a rare mutation in the CFTR gene (p.R347H). CFTR mutations are the most common cause of CBAVD and have also been linked to CUAVD. However, this is a unique case of two brothers with the same genetic mutation but different phenotypic expressions of the mutation. Conclusions We have identified a rare CFTR variant (p.R347H) in two brothers with different reproductive capacities. We present evidence that absence of the vas deferens (unilateral or bilateral) may be associated with CFTR mutations, even in the absence of diagnosed cystic fibrosis. Understanding the phenotypic spectrum of CFTR gene mutations is pivotal to treating associated male infertility. Disclosure Any of the authors act as a consultant, employee or shareholder of an industry for: Acerus Pharmaceuticals, Boston Scientific, Coloplast, Endo Pharmaceuticals, Empower Pharmacy, Nestle Health, Olympus, Hims Inc.