Partial DAZ deletions in a family with five infertile brothers.
OBJECTIVE
To study the genetic cause of infertility in a family with five infertile brothers.


METHODS
Case report.


METHODS
Center for reproductive medicine at a university medical center.


METHODS
Five brothers presenting with primary infertility due to severely impaired spermatogenesis; also, their parents and two other paternally related family members.


METHODS
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.


METHODS
DAZ gene copy number, X chromosome linkage, and mtDNA sequence.


RESULTS
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.


CONCLUSIONS
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.
Gianotten
Judith
J
Center for Reproductive Medicine, Academic Medical Center, The, Amsterdam, Netherlands. j.gianotten@amc.uva.nl
Hoffer
Mariëtte J V
MJ
De Vries
Jan W A
JW
Leschot
Nico J
NJ
Gerris
Jan
J
van der Veen
Fulco
F
D000328:Adult; D000075364:Deleted in Azoospermia 1 Protein; D017353:Gene Deletion; D008040:Genetic Linkage; D006801:Humans; D007248:Infertility, Male / Q000235:genetics*; D008297:Male; D016601:RNA-Binding Proteins / Q000235:genetics*
C095668:DAZ1 protein, human; D000075364:Deleted in Azoospermia 1 Protein; D016601:RNA-Binding Proteins