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1: Hum Mutat. 2007 Jan;28(1):98.

Microsatellite in the 3' untranslated region of human fibroblast growth factor 9 
(FGF9) gene exhibits pleiotropic effect on modulating FGF9 protein expression.

Chen TM, Kuo PL, Hsu CH, Tsai SJ, Chen MJ, Lin CW, Sun HS.

Institute of Basic Medical Sciences, National Cheng Kung University Medical
College, Tainan, Taiwan.

Fibroblast growth factor 9 (FGF9) is a member of secreted polypeptide families
and involved in many important biological processes, including implantation and
morphogenesis during embryogenesis and adult life. Recently, Fgf9-knockout mice
exhibited male-to-female sex reversal, demonstrating a novel function for FGF9 in
testicular development. We hypothesized that FGF9 is involved in sex development 
at an early embryonic stage in humans. In this study, we systematically screened 
sequences of the FGF9 gene in 21 XY females and 72 XX females and XY males to
examine whether sequence variants of the FGF9 gene play a pathophysiological role
on human gonadal dysgenesis. No mutation was identified, but a single nucleotide 
variant and two microsatellites were found. The allelic distribution of
polymorphic microsatellite in the 3'-UTR of FGF9 between patients and controls
was slightly different with Bonferroni correction (P=0.06). We further applied
reporter gene system and quantitative RT-PCR to study the function of this
microsatellite motif and results demonstrated that the (TG)(n) motif modulated
gene expression at both pre- and post-transcriptional levels. The (TG)(14)
allele, which showed a potential association with male-to-female sex reversal
(odds ratio=6.08, 95% confidence interval=1.39-26.63), displayed the strongest
promoter activity and longest mRNA stability. These data demonstrated that 3'-UTR
microsatellite of the FGF9 is a functional polymorphism that plays dual roles in 
regulating FGF9 expression. Although our preliminary result suggested a possible 
association between FGF9 and human gonadal dysgenesis, the major limitation of
small dataset in this study points out the requirement for further investigation.

PMID: 17154280 [PubMed - indexed for MEDLINE]

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