Objective: To determine whether mutations in the pro-hAKAP82 gene and the resulting pro-hAKAP82 and hAKAP82 proteins were associated with the infertility seen in a patient with stump tail sperm.
Design: Case report.
Setting: Academic research and teaching environment, tertiary care hospital.
Patient(s): A single, infertile Caucasian male diagnosed with essentially 100% stump tail sperm.
Intervention(s): None.
Main outcome measure(s): Electrophoresis, silver staining, and immunoblotting of patient and control sperm proteins; RII (type II regulatory subunit of protein kinase-A) overlay assay of patient and control sperm proteins, partial DNA sequence analysis of patient's pro-hAKAP82 gene; indirect immunofluorescence and immunogold electron microscopy of patient and control sperm.
Results(s): No significant abnormalities in the size or amount of pro-hAKAP82 and hAKAP82 or in the ability of these proteins to bind the regulatory subunit of protein kinase-A were identified in the patient's sperm. Partial sequence analysis of the patient's pro-hAKAP82 gene was identical to the published normal sequence. Indirect immunofluorescence and immunoelectron microscopy of sperm localized pro-hAKAP82/hAKAP82 to the sperm flagellum and demonstrated that the proteins were present in a disorganized, amorphous region, which apparently represented the fibrous sheath.
Conclusion(s): These results suggest that, although pro-hAKAP82 and hAKAP82 localize to the correct structural component of the flagellum and are not directly responsible for the stump tail phenotype, they are unable to assemble normally into the fibrous sheath. Although this study did not identify abnormalities in the pro-hAKAP82 gene or its resulting proteins in a patient with stump tail sperm, several regions of the gene and protein remain to be examined.