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 journalArticle

98 Citations (Scopus)

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

Fingerprint

Kallmann Syndrome
Transcription Factors
Proteins
Missense Mutation
Puberty
Genes
Neurons
Idiopathic Hypogonadotropic Hypogonadism

ASJC Scopus subject areas

  • Genetics
  • Genetics(clinical)

Cite this

WDR11, a WD protein that interacts with transcription factor EMX1, is mutated in idiopathic hypogonadotropic hypogonadism and Kallmann syndrome. / Kim, Hyung Goo; Ahn, Jang Won; Kurth, Ingo; Ullmann, Reinhard; Kim, Hyun Taek; Kulharya, Anita; Ha, Kyung Soo; Itokawa, Yasuhide; Meliciani, Irene; Wenzel, Wolfgang; Lee, Deresa; Rosenberger, Georg; Ozata, Metin; Bick, David P.; Sherins, Richard J.; Nagase, Takahiro; Tekin, Mustafa; Kim, Soo Hyun; Kim, Cheol Hee; Ropers, Hans Hilger; Gusella, James F.; Kalscheuer, Vera; Choi, Cheol Yong; Layman, Lawrence C.

In: American journal of human genetics, Vol. 87, No. 4, 08.10.2010, p. 465-479.

Research output: Contribution to journalArticle

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 2010, 'WDR11, a WD protein that interacts with transcription factor EMX1, is mutated in idiopathic hypogonadotropic hypogonadism and Kallmann syndrome', American journal of human genetics, vol. 87, no. 4, pp. 465-479. https://doi.org/10.1016/j.ajhg.2010.08.018
Kim, Hyung Goo ; Ahn, Jang Won ; Kurth, Ingo ; Ullmann, Reinhard ; Kim, Hyun Taek ; Kulharya, Anita ; Ha, Kyung Soo ; Itokawa, Yasuhide ; Meliciani, Irene ; Wenzel, Wolfgang ; Lee, Deresa ; Rosenberger, Georg ; Ozata, Metin ; Bick, David P. ; Sherins, Richard J. ; Nagase, Takahiro ; Tekin, Mustafa ; Kim, Soo Hyun ; Kim, Cheol Hee ; Ropers, Hans Hilger ; Gusella, James F. ; Kalscheuer, Vera ; Choi, Cheol Yong ; Layman, Lawrence C. / WDR11, a WD protein that interacts with transcription factor EMX1, is mutated in idiopathic hypogonadotropic hypogonadism and Kallmann syndrome. In: American journal of human genetics. 2010 ; Vol. 87, No. 4. pp. 465-479.
@article{3c364e324baf44e3814699203f96025c,
title = "WDR11, a WD protein that interacts with transcription factor EMX1, is mutated in idiopathic hypogonadotropic hypogonadism and Kallmann syndrome",
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.",
author = "Kim, {Hyung Goo} and Ahn, {Jang Won} and Ingo Kurth and Reinhard Ullmann and Kim, {Hyun Taek} and Anita Kulharya and Ha, {Kyung Soo} and Yasuhide Itokawa and Irene Meliciani and Wolfgang Wenzel and Deresa Lee and Georg Rosenberger and Metin Ozata and Bick, {David P.} and Sherins, {Richard J.} and Takahiro Nagase and Mustafa Tekin and Kim, {Soo Hyun} and Kim, {Cheol Hee} and Ropers, {Hans Hilger} and Gusella, {James F.} and Vera Kalscheuer and Choi, {Cheol Yong} and Layman, {Lawrence C.}",
year = "2010",
month = "10",
day = "8",
doi = "10.1016/j.ajhg.2010.08.018",
language = "English (US)",
volume = "87",
pages = "465--479",
journal = "American Journal of Human Genetics",
issn = "0002-9297",
publisher = "Cell Press",
number = "4",

}

TY - JOUR

T1 - WDR11, a WD protein that interacts with transcription factor EMX1, is mutated in idiopathic hypogonadotropic hypogonadism and Kallmann syndrome

AU - Kim, Hyung Goo

AU - Ahn, Jang Won

AU - Kurth, Ingo

AU - Ullmann, Reinhard

AU - Kim, Hyun Taek

AU - Kulharya, Anita

AU - Ha, Kyung Soo

AU - Itokawa, Yasuhide

AU - Meliciani, Irene

AU - Wenzel, Wolfgang

AU - Lee, Deresa

AU - Rosenberger, Georg

AU - Ozata, Metin

AU - Bick, David P.

AU - Sherins, Richard J.

AU - Nagase, Takahiro

AU - Tekin, Mustafa

AU - Kim, Soo Hyun

AU - Kim, Cheol Hee

AU - Ropers, Hans Hilger

AU - Gusella, James F.

AU - Kalscheuer, Vera

AU - Choi, Cheol Yong

AU - Layman, Lawrence C.

PY - 2010/10/8

Y1 - 2010/10/8

N2 - 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.

AB - 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.

UR - http://www.scopus.com/inward/record.url?scp=77957739987&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=77957739987&partnerID=8YFLogxK

U2 - 10.1016/j.ajhg.2010.08.018

DO - 10.1016/j.ajhg.2010.08.018

M3 - Article

C2 - 20887964

AN - SCOPUS:77957739987

VL - 87

SP - 465

EP - 479

JO - American Journal of Human Genetics

JF - American Journal of Human Genetics

SN - 0002-9297

IS - 4

ER -