• PMID: 20887964
• Gene Name: WDR11
• Condition: Idiopathic hypogonadotropic hypogonadism, Kallmann syndrome
• Association: The findings suggest that impaired pubertal development in these patients results from a deficiency of productive WDR11 protein interaction.
• Mutation: A435T, R448Q, and H690Q
• Population size: 6
• Population details: 6 idiopathic hypogonadotropic hypogonadism, Kallmann syndrome
• Sex: Male, Female
• Infertility type: Male infertility, Female infertility
• Associated genes: EMX1, WDR11
• Other associated phenotypes: Idiopathic hypogonadotropic hypogonadism, Kallmann syndrome

WDR11, a WD protein that interacts with transcription factor EMX1, is mutated in idiopathic hypogonadotropic hypogonadism and Kallmann syndrome

Kim HG, Ahn JW, Kurth I, Ullmann R, Kim HT, Kulharya A, Ha KS, Itokawa Y, Meliciani I, Wenzel W, Lee D, Rosenberger G, Ozata M, Bick DP, Sherins RJ, Nagase T, Tekin M, Kim SH, Kim CH, Ropers HH, Gusella JF, Kalscheuer V, Choi CY, Layman LC.

By defining the chromosomal breakpoint of a balanced t(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 β 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. CI - Copyright © 2010 The American Society of Human Genetics. Published by Elsevier Inc. All rights reserved. FAU - Kim, Hyung-Goo AU - Kim HG AD - Section of Reproductive Endocrinology, Infertility, and Genetics, Department of Obstetrics and Gynecology, Medical College of Georgia, 1120 15th Street, Augusta, Georgia 30912, USA. hkim@chgr.mgh.harvard.edu FAU - Ahn, Jang-Won AU - Ahn JW FAU - Kurth, Ingo AU - Kurth I FAU - Ullmann, Reinhard AU - Ullmann R FAU - Kim, Hyun-Taek AU - Kim HT FAU - Kulharya, Anita AU - Kulharya A FAU - Ha, Kyung-Soo AU - Ha KS FAU - Itokawa, Yasuhide AU - Itokawa Y FAU - Meliciani, Irene AU - Meliciani I FAU - Wenzel, Wolfgang AU - Wenzel W FAU - Lee, Deresa AU - Lee D FAU - Rosenberger, Georg AU - Rosenberger G FAU - Ozata, Metin AU - Ozata M FAU - Bick, David P AU - Bick DP FAU - Sherins, Richard J AU - Sherins RJ FAU - Nagase, Takahiro AU - Nagase T FAU - Tekin, Mustafa AU - Tekin M FAU - Kim, Soo-Hyun AU - Kim SH FAU - Kim, Cheol-Hee AU - Kim CH FAU - Ropers, Hans-Hilger AU - Ropers HH FAU - Gusella, James F AU - Gusella JF FAU - Kalscheuer, Vera AU - Kalscheuer V FAU - Choi, Cheol Yong AU - Choi CY