Genetics of Vas Aplasia
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Congenital bilateral absence of the vas deferens (CBAVD) involves a complete or partial defect of the Wolffian duct derivatives and is a common cause of obstructive azoospermia. There are different subphenotypes of CAVD such as congenital bilateral absence of vas deferens (CBAVD), congenital unilateral absence of vas deferens (CUAVD), and CBAVD/CUAVD associated with renal anomalies. 95% of men with cystic fibrosis have CBAVD, while 60–70% of men with isolated CBAVD have detectable mutations in the cystic fibrosis transmembrane conductance regulator (CFTR) gene. Failure to detect a CFTR abnormality in these men could be due to limitations of the mutation detection methods or due to an etiology other than CFTR gene. The CFTR mutations have been traditionally classified into six classes based on clinical severity of CFTR mutations. Majority of CBAVD men have one severe and one mild CFTR mutation or two mild CFTR mutations. A proportion of CBAVD men (11–20%) suffer from concomitant urogenital abnormalities. CFTR mutations are generally not detected in these men, and other genetic causes are postulated. The type and severity of mutation vary with geography and ethnicity. Current ASRM, ACOG, and ACMG recommendations for genetic diagnosis or risk prediction of CBAVD have limitations, and there is a need to develop regional guidelines based on the ethnic-specific CFTR mutation screening. We describe the clinical presentation, diagnosis, and CFTR abnormalities detected in different subphenotypes of CAVD.
KeywordsVas aplasia Genetics Cystic fibrosis Azoospermia CFTR CBAVD CUAVD CFTR Renal anomalies Genetic counseling
Dr. Smita Mahale, Director, ICMR-NIRRH, Mumbai; Dr. Vijay Kulkarni, Consultant Andrologist, ICMR-NIRRH; Mr. Vaibhav Shinde, Technician A, ICMR-NIRRH; and Ms. Aishwarya Bhurke, Project Assistant are sincerely acknowledged.
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