Objective: To study the genetic cause of infertility in a family with five infertile brothers.
Design: Case report.
Settings: Center for reproductive medicine at a university medical center.
Patient(s): Five brothers presenting with primary infertility due to severely impaired spermatogenesis; also, their parents and two other paternally related family members.
Intervention(s): Fluorescence in situ hybridization and sequence family variant analysis was performed in leukocyte DNA to determine the number of deleted in azoospermia (DAZ) genes. Linkage analysis was performed for X chromosome inheritance, and mitochondrial DNA (mtDNA) was screened for mutations.
Main outcome measure(s): DAZ gene copy number, X chromosome linkage, and mtDNA sequence.
Result(s): With conventional polymerase chain reaction (PCR) analysis, no deletions of the AZFc region were found, but with fluorescence in situ hybridization and sequence family variant analysis, only two DAZ genes instead of four were detected in all individuals tested. The five brothers did not share an identical X chromosomal locus, and no mutations were found in the mtDNA of the index patient.
Conclusion(s): A reduced copy number of the DAZ genes is found in five infertile brothers with severely impaired spermatogenesis, as well as in their normospermic father and in two other fertile paternally related family members. This illustrates that the phenotype associated with a reduced copy number of the DAZ genes can be extremely variable.