title: NOBOX homeobox mutation causes premature ovarian failure.
abstract: 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.
authors: Center for Reproductive Medicine, Shandong Provincial Hospital of Shandong University, Jinan, China.
authors: Yingying
authors: Y
authors: Qin
authors: Youngsok
authors: Y
authors: Choi
authors: Han
authors: H
authors: Zhao
authors: Joe Leigh
authors: JL
authors: Simpson
authors: Zi-Jiang
authors: ZJ
authors: Chen
authors: Aleksandar
authors: A
authors: Rajkovic
mesh_terms: 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*
chemical_list: D018398:Homeodomain Proteins; C506600:NOBOX protein, human; D014157:Transcription Factors; D001120:Arginine
references: Mol Endocrinol. 1999 Nov;13(11):1844-54
references: 10551778
references: Fertil Steril. 2007 Mar;87(3):456-65
references: 17074338
references: Nat Genet. 2001 Feb;27(2):132-4
references: 11175772
references: Nucleic Acids Res. 2001 Aug 1;29(15):3258-69
references: 11470884
references: Mech Dev. 2002 Feb;111(1-2):137-41
references: 11804785
references: Mol Hum Reprod. 2002 Apr;8(4):311-7
references: 11912278
references: Proc Natl Acad Sci U S A. 2003 Mar 18;100(6):3119-24
references: 12626758
references: J Biol Chem. 2003 Jul 25;278(30):27532-9
references: 12746429
references: Am J Hum Genet. 2004 Jul;75(1):106-11
references: 15136966
references: Science. 2004 Aug 20;305(5687):1157-9
references: 15326356
references: Obstet Gynecol. 1986 Apr;67(4):604-6
references: 3960433
references: Cell. 1995 Sep 22;82(6):959-68
references: 7553856
references: Hum Reprod. 1998 Jul;13(7):1796-800
references: 9740426
references: Hum Reprod. 2005 Feb;20(2):402-12
references: 15608041
references: Nucleic Acids Res. 2005;33(8):2661-75
references: 15886395
references: Fertil Steril. 2005 Jun;83(6):1843-4
references: 15950662
references: Hum Reprod Update. 2006 Jan-Feb;12(1):65-76
references: 16143663
references: Proc Natl Acad Sci U S A. 2006 Jan 3;103(1):224-9
references: 16373508
references: Cell Mol Life Sci. 2006 Mar;63(5):579-90
references: 16416028
references: Aust N Z J Obstet Gynaecol. 2006 Jun;46(3):242-4
references: 16704481
references: Mol Hum Reprod. 2006 May;12(5):283-9
references: 16597639
references: Mol Endocrinol. 2006 Jun;20(6):1406-22
references: 16513794
references: Am J Hum Genet. 2006 Jul;79(1):113-9
references: 16773570
references: J Mol Biol. 2006 Jul 28;360(5):989-99
references: 16814806
references: Development. 2006 Nov;133(22):4527-37
references: 17050619
references: J Biol Chem. 2006 Nov 24;281(47):35747-56
references: 16997917
references: Endocrinology. 2007 Jan;148(1):393-400
references: 17038554
references: Hum Genet. 2007 Mar;121(1):107-12
references: 17089161
references: Curr Med Chem. 2007;14(3):353-7
references: 17305537
references: Am J Med Genet. 1999 Dec 29;89(4):186-200
references: 10727994