Mutation analysis of two candidate genes for premature ovarian failure, DACH2 and POF1B.
BACKGROUND
Balanced X;autosome translocations interrupting the 'critical region' of the long arm of the human X chromosome are often associated with premature ovarian failure (POF). However, the mechanisms leading to X-linked ovarian dysfunction are largely unknown, as the majority of the X chromosome breakpoints have been mapped to gene-free genomic regions. A few genes have been found to be interrupted, but their role has never been clarified.


RESULTS
By fine mapping of the X chromosome breakpoint of an X;autosome balanced translocation, we identified a new interrupted gene, POF1B. We performed a mutation analysis of POF1B and of another gene previously identified, DACH2, localized approximately 700 kb distal in Xq21, in a cohort of >200 Italian POF patients. Rare mutations were found in patients in both genes.


CONCLUSIONS
Our findings could not demonstrate any involvement of POF1B, but suggest that rare mutations in the DACH2 gene may have a role in the POF phenotype.
Bione
S
S
Institute of Molecular Genetics-CNR, 27100 Pavia, Italy.
Rizzolio
F
F
Sala
C
C
Ricotti
R
R
Goegan
M
M
Manzini
M C
MC
Battaglia
R
R
Marozzi
A
A
Vegetti
W
W
Dalprà
L
L
Crosignani
P G
PG
Ginelli
E
E
Nappi
R
R
Bernabini
S
S
Bruni
V
V
Torricelli
F
F
Zuffardi
O
O
Toniolo
D
D
D000293:Adolescent; D000328:Adult; D000595:Amino Acid Sequence; D002648:Child; D041321:Chromosomes, Human, X; D004252:DNA Mutational Analysis; D004268:DNA-Binding Proteins; D004303:Dosage Compensation, Genetic; D005260:Female; D014644:Genetic Variation; D006801:Humans; D008840:Microfilament Proteins / Q000235:genetics*; D008875:Middle Aged; D008969:Molecular Sequence Data; D009154:Mutation; D009687:Nuclear Proteins / Q000235:genetics*; D016649:Primary Ovarian Insufficiency / Q000235:genetics*; D011506:Proteins / Q000235:genetics*; D014157:Transcription Factors; D014178:Translocation, Genetic
C403064:DACH2 protein, human; D004268:DNA-Binding Proteins; D008840:Microfilament Proteins; D009687:Nuclear Proteins; C500687:POF1B protein, human; C519668:POF1B protein, mouse; D011506:Proteins; D014157:Transcription Factors