NOBOX homeobox mutation causes premature ovarian failure.
NOBOX (newborn ovary homeobox gene) is an oocyte-specific homeobox gene that plays a critical role in early folliculogenesis and represents a candidate gene for nonsyndromic ovarian failure. We investigated whether mutations in the NOBOX gene cause premature ovarian failure (POF). We sequenced the NOBOX gene in 96 white women with POF and discovered seven known single-nucleotide polymorphisms and four novel variations, two of which, p.Arg355His and p.Arg360Gln, cause missense mutations in the homeobox domain. Electrophoretic mobility shift assay (EMSA) confirmed that the missense mutation, p.Arg355His, disrupted NOBOX homeodomain binding to NOBOX DNA-binding element (NBE) and had a dominant negative effect on the binding of wild-type NOBOX to DNA. Our findings demonstrate that NOBOX mutations can cause POF.
Qin
Yingying
Y
Center for Reproductive Medicine, Shandong Provincial Hospital of Shandong University, Jinan, China.
Choi
Youngsok
Y
Zhao
Han
H
Simpson
Joe Leigh
JL
Chen
Zi-Jiang
ZJ
Rajkovic
Aleksandar
A
D000328:Adult; D000595:Amino Acid Sequence; D019943:Amino Acid Substitution / Q000235:genetics; D001120:Arginine / Q000737:chemistry / Q000235:genetics; D005260:Female; D018398:Homeodomain Proteins / Q000235:genetics*; D006801:Humans; D008969:Molecular Sequence Data; D009154:Mutation; D016649:Primary Ovarian Insufficiency / Q000235:genetics*; D014157:Transcription Factors / Q000235:genetics*
D018398:Homeodomain Proteins; C506600:NOBOX protein, human; D014157:Transcription Factors; D001120:Arginine
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