WDR11, a WD Protein that Interacts with Transcription Factor EMX1, Is Mutated in Idiopathic Hypogonadotropic Hypogonadism and Kallmann Syndrome

被引：130

作者：

Kim, Hyung-Goo ^{[1
,2
,5
,19
,20
]}

Ahn, Jang-Won ^{[3
]}

Kurth, Ingo ^{[4
,21
]}

Ullmann, Reinhard ^{[5
]}

Kim, Hyun-Taek ^{[6
,7
]}

Kulharya, Anita ^{[8
,9
]}

Ha, Kyung-Soo ^{[10
]}

Itokawa, Yasuhide ^{[11
]}

Meliciani, Irene ^{[12
]}

Wenzel, Wolfgang ^{[12
]}

Lee, Deresa ^{[3
]}

Rosenberger, Georg ^{[4
]}

Ozata, Metin ^{[13
]}

Bick, David P. ^{[14
,15
]}

Sherins, Richard J. ^{[16
]}

Nagase, Takahiro ^{[11
]}

Tekin, Mustafa ^{[17
,22
]}

Kim, Soo-Hyun ^{[18
]}

Kim, Cheol-Hee ^{[6
,7
]}

Ropers, Hans-Hilger ^{[5
]}

Gusella, James F. ^{[19
,20
]}

Kalscheuer, Vera ^{[5
]}

Choi, Cheol Yong ^{[3
]}

Layman, Lawrence C. ^{[1
,2
]}

机构：

[1] Med Coll Georgia, Sect Reprod Endocrinol Infertil & Genet, Reprod Med & Dev Neurobiol Programs, Dept Obstet & Gynecol,Inst Mol Med & Genet, Augusta, GA 30912 USA

[2] Med Coll Georgia, Neurosci Program, Augusta, GA 30912 USA

[3] Sungkyunkwan Univ, Dept Biol Sci, Suwon 440746, South Korea

[4] Univ Klinikum Hamburg Eppendorf, Inst Humangenet, D-20246 Hamburg, Germany

[5] Max Planck Inst Mol Genet, Dept Human Mol Genet, D-14195 Berlin, Germany

[6] Chungnam Natl Univ, Dept Biol, Taejon 305764, South Korea

[7] Chungnam Natl Univ, Grad Sch Analyt Sci & Technolgy, Taejon 305764, South Korea

[8] Med Coll Georgia, Dept Pediat, Augusta, GA 30912 USA

[9] Med Coll Georgia, Dept Pathol, Augusta, GA 30912 USA

[10] Med Coll Georgia, Ctr Canc, Augusta, GA 30912 USA

[11] Kazusa DNA Res Inst, Dept Human Genome Res, Chiba 2920818, Japan

[12] Forschungszentrum Karlsruhe, Inst Nanotechnol, D-76021 Karlsruhe, Germany

[13] Gulhane Mil Med Acad, Haydarpasa Training Hosp, Dept Endocrinol, TR-34660 Istanbul, Turkey

[14] Med Coll Wisconsin, Div Med Genet, Dept Pediat, Milwaukee, WI 53226 USA

[15] Med Coll Wisconsin, Dept Obstet & Gynecol, Milwaukee, WI 53226 USA

[16] Columbia Fertil Associates, Washington, DC 20037 USA

[17] Univ Miami, Dr John T Macdonald Fdn, Dept Human Genet, Miller Sch Med, Miami, FL 33156 USA

[18] Univ London, Div Basic Med Sci, St Georges Med Sch, London SW17 0RE, England

[19] Harvard Univ, Sch Med, Ctr Human Genet Res, Massachusetts Gen Hosp, Boston, MA 02114 USA

[20] Harvard Univ, Sch Med, Dept Genet, Boston, MA 02114 USA

[21] Jena Univ Hosp, Inst Human Genet, D-07743 Jena, Germany

[22] Ankara Univ, Sch Med, Div Pediat Genet, TR-06610 Ankara, Turkey

来源：

AMERICAN JOURNAL OF HUMAN GENETICS | 2010年 / 87卷 / 04期

基金：

美国国家卫生研究院;

关键词：

GONADOTROPIN-RELEASING-HORMONE; METASTASIS SUPPRESSOR GENE; TERMINAL DELETION; EMPTY-SPIRACLES; MUTATIONS; TRANSLOCATION; EXPRESSION; RECEPTOR; IDENTIFICATION; HYBRIDIZATION;

D O I：

10.1016/j.ajhg.2010.08.018

中图分类号：

Q3 [遗传学];

学科分类号：

071007 ; 090102 ;

摘要：

By defining the chromosomal breakpoint of a balanced 1(10,12) translocation from a subject with Kallmann syndrome and scanning genes in its vicinity in unrelated hypogonadal subjects, we have identified WDR11 as a gene involved in human puberty We found six patients with a total of five different heterozygous WDR11 missense mutations, including three alterations (A435T, R448Q and H690Q) in WD domains important for beta propeller formation and protein-protein interaction In addition, we discovered that WDR11 interacts with EMX1, a homeodomain transcription factor involved in the development of olfactory neurons, and that missense alterations reduce or abolish this interaction. Our findings suggest that impaired pubertal development in these patients results from a deficiency of productive WDR11 protein interaction

引用

页码：465 / 479

页数：15

共 59 条

[1] 10, 15 reciprocal translocation in an infertile man: ultrastructural and fluorescence in-situ hybridization sperm study: Case report [J].