Compound genetic abnormalities in patients with cystic fibrosis transmembrane regulator gene mutation.

Objective: To determine the prevalence of compound genetic abnormalities in patients who are carriers of cystic fibrosis mutations.

Design: Case report.

Setting: Tertiary referral center for male infertility.

Patient(s): Between 2000 and 2005, 65 patients were identified to be carriers of cystic fibrosis transmembrane regulator gene (CFTR) mutations or have a polymorphism of the polythymidine tract of intron 8.

Intervention(s): Patients were evaluated for male factor infertility. Additional genetic testing for karyotype abnormalities or Y chromosome microdeletions was performed when indicated because of evidence of impaired spermatogenesis during surgical sperm retrieval or on semen analysis. A comparison of similar patients is in the published literature.

Main Outcome Measure(s): Characteristics of patients with compound genetic abnormalities presenting to an academic male fertility practice. Comparison to similar patients reported in the literature.

Result(s): Two patients (3.1%) out of 65 were identified in our database to have compound genetic abnormalities. One patient had a W1282X mutation while the other had an I148T mutation. Both patients had deletions of AZF b + c regions. There were no karyotype abnormalities identified in our database. An additional two patients with compound CFTR mutations and Y chromosome microdeletions were identified in the literature. Three patients in the literature had compound CFTR mutations and karyotype abnormalities.

Conclusion: Compound genetic abnormalities in CFTR mutation patients can be a contributing factor when abnormal spermatogenesis is encountered. A secondary genetic etiology should be considered in these types of patients.