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.