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

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

Research output: Contribution to journalArticlepeer-review

149 Scopus citations

Abstract

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.

Original languageEnglish (US)
Pages (from-to)465-479
Number of pages15
JournalAmerican journal of human genetics
Volume87
Issue number4
DOIs
StatePublished - Oct 8 2010

ASJC Scopus subject areas

  • Genetics
  • Genetics(clinical)

Fingerprint

Dive into the research topics of 'WDR11, a WD protein that interacts with transcription factor EMX1, is mutated in idiopathic hypogonadotropic hypogonadism and Kallmann syndrome'. Together they form a unique fingerprint.

Cite this