Mutational analysis of the human FATE gene in 144 infertile men.
The FATE gene maps to Xq28 where one case of a translocation breakpoint has been found in an infertile man. Moreover, the FATE promoter contains a putative SF-1-binding site, and FATE has been proposed as representing a target gene of SF-1 in testicular development or germ cell differentiation. This study presents a complete mutational screening of the FATE gene in a random group of 144 infertile males. Four polymorphisms and two mutations were found. Three of the polymorphisms, viz., 741C-->T, 905A-->C, and 3985C-->T, occurred in exon 5 and intron 2 and did not alter the deduced polypeptide. One polymorphism resulted in the conservative amino acid exchange, A10 V, in 16.0% of the patients. This substitution occurred with similar frequencies in the control groups, indicating that the mutation does not affect fertility in men or women. The two mutations caused the non-conservative amino acid substitutions S125R (patient 1) and I34T (patient 2). A family study (patient 1) revealed, however, that S125R was inherited and that a fertile male family member carried the mutation. Patient 2 did not have relevant family members who could be examined. Thus, this study has shown that only 1.4% of infertile men have mutations in the FATE gene, and that some of these mutations do not singly cause infertility. Hence, FATE may not play an important role in the disease-state of infertile men attending fertility clinics. However, FATE mutations cannot be excluded as being a contributing factor in some cases of male infertility.
Olesen
Christian
C
Laboratory of Reproductive Biology, Rigshospitalet, DK-2100, Copenhagen, Denmark. c.olesen@mail.tele.dk
Silber
Joachim
J
Eiberg
Hans
H
Ernst
Erik
E
Petersen
Karsten
K
Lindenberg
Svend
S
Tommerup
Niels
N
D000328:Adult; D000409:Alanine / Q000235:genetics; D000595:Amino Acid Sequence; D000818:Animals; D001120:Arginine / Q000235:genetics; D003545:Cysteine / Q000235:genetics; D004252:DNA Mutational Analysis; D017931:DNA Primers; D004268:DNA-Binding Proteins / Q000235:genetics*; D005091:Exons / Q000235:genetics; D006801:Humans; D007248:Infertility, Male / Q000235:genetics*; D007438:Introns / Q000235:genetics; D007621:Karyotyping; D008297:Male; D008969:Molecular Sequence Data; D009154:Mutation; D010375:Pedigree; D016133:Polymerase Chain Reaction; D011110:Polymorphism, Genetic; D012694:Serine / Q000235:genetics; D013912:Threonine / Q000235:genetics; D014157:Transcription Factors / Q000235:genetics*; D014960:X Chromosome / Q000235:genetics*
D017931:DNA Primers; D004268:DNA-Binding Proteins; C449758:FATE1 protein, human; D014157:Transcription Factors; D013912:Threonine; D012694:Serine; D001120:Arginine; D003545:Cysteine; D000409:Alanine