Novel missense mutations of the Deleted-in-AZoospermia-Like (DAZL) gene in infertile women and men.
BACKGROUND
The Deleted-in-AZoospermia-Like (DAZL) gene has homologs required for germ cell development in many organisms. Recently, we showed that there are several common polymorphisms within the DAZL gene that are associated with age at ovarian failure/menopause and sperm count.


METHODS
Here we sought to identify rare mutations in DAZL and examine their phenotypes in men and women. We sequenced the DAZL gene in 519 individuals; sequences spanned the entire coding region of the gene.


RESULTS
We report the identification of four putative missense mutations in DAZL. Three individuals that were heterozygous for a DAZL mutation reported having children, while two individuals that were homozygous reported no children. These mutations were found only in infertile men and women.


CONCLUSIONS
Given the strong data associating DAZL polymorphisms and deletions with fertility in humans and model organisms, we suggest that these mutations may be associated with age at menopause and/or sperm count and warrant further biochemical and genetic investigation.
Tung
Joyce Y
JY
Human Embryonic Stem Cell Center, Department of Obstetrics, Gynecology, and Reproductive Sciences, University of California at San Francisco, San Francisco, CA 94143, USA. joyce.tung@stanford.edu
Rosen
Mitchell P
MP
Nelson
Lawrence M
LM
Turek
Paul J
PJ
Witte
John S
JS
Cramer
Daniel W
DW
Cedars
Marcelle I
MI
Reijo-Pera
Renee A
RA
D000293:Adolescent; D000328:Adult; D005260:Female; D006579:Heterozygote; D006720:Homozygote; D006801:Humans; D007247:Infertility, Female / Q000235:genetics*; D007248:Infertility, Male / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D020125:Mutation, Missense; D010298:Parity; D011247:Pregnancy; D016649:Primary Ovarian Insufficiency / Q000235:genetics; D016601:RNA-Binding Proteins / Q000235:genetics*
C101358:DAZL protein, human; D016601:RNA-Binding Proteins