Characterization and mutation analysis of the human formin-2 (FMN2) gene in women with unexplained infertility.
OBJECTIVE
Formin-2 (Fmn2) mutant mice produce oocytes with meiosis I arrest. Our aim was to describe the human FORMIN-2 (FMN2) gene and to identify DNA sequence polymorphisms in patients with unexplained infertility and multiple failed IVF cycles.


METHODS
Institutional review board-approved observational case-control study.


METHODS
Infertility center and university hospital.


METHODS
Sixty-two fertile controls and seven subjects with unexplained infertility.


METHODS
BLASTP (www.ncbi.nlm.nih.gov) was used to map the genomic DNA and complementary DNA sequence of FMN2. Genomic DNA was extracted from blood leukocyte samples. The polymerase chain reaction was used to amplify FMN2 gene exons for analysis by denaturing gradient gel electrophoresis.


METHODS
Characterization of the FMN2 gene and identification of fragment melting polymorphisms (FMPs).


RESULTS
FMN2 includes 411,960 base pairs (bp) of DNA with 6,204 bp in 18 exons. There was no difference in FMN2 FMP allele frequencies between the controls and subjects. One patient was homozygous for one FMP.


CONCLUSIONS
The human FMN2 gene is conserved between evolutionarily diverse vertebrates. It is likely that FMN2 has the same function as Fmn2 in the mouse (i.e., maintenance of the meiotic spindle). Prospective identification of patients with meiosis I arrest is necessary to determine whether FMN2 mutations are a cause of unexplained infertility.
Ryley
David A
DA
Boston IVF, Waltham, Massachusetts 02215, USA. dryley@bidmc.harvard.edu
Wu
Hsin-Hung
HH
Leader
Benjamin
B
Zimon
Alison
A
Reindollar
Richard H
RH
Gray
Mark R
MR
D000328:Adult; D000818:Animals; D016022:Case-Control Studies; D004252:DNA Mutational Analysis / Q000379:methods; D005260:Female; D005787:Gene Frequency / Q000235:genetics; D005796:Genes / Q000502:physiology*; D006801:Humans; D007247:Infertility, Female / Q000175:diagnosis / Q000235:genetics* / Q000473:pathology; D008540:Meiosis / Q000235:genetics; D051379:Mice; D009419:Nerve Tissue Proteins / Q000737:chemistry / Q000235:genetics*; D016133:Polymerase Chain Reaction / Q000379:methods
D009419:Nerve Tissue Proteins