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

2010; Elsevier BV; Volume: 87; Issue: 4 Linguagem: Inglês

10.1016/j.ajhg.2010.08.018

1537-6605

Hyung‐Goo Kim, Jang-Won Ahn, Ingo Kurth, Reinhard Ullmann, Hyun-Taek Kim, Anita S. Kulharya, Kyung-Soo Ha, Yasuhide Itokawa, Irene Meliciani, Wolfgang Wenzel, Deresa Lee, Georg Rosenberger, Metin Özata, David Bick, Richard J. Sherins, Takahiro Nagase, Mustafa Tekin, Soo‐Hyun Kim, Cheol‐Hee Kim, Hans‐Hilger Ropers, James F. Gusella, Vera M. Kalscheuer, Cheol Yong Choi, Lawrence C. Layman,

Plant Reproductive Biology

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.