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.
authors.affiliation: 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
authors.forename: Hyung-Goo
authors.initials: HG
authors.lastname: Kim
authors.forename: Jang-Won
authors.initials: JW
authors.lastname: Ahn
authors.forename: Ingo
authors.initials: I
authors.lastname: Kurth
authors.forename: Reinhard
authors.initials: R
authors.lastname: Ullmann
authors.forename: Hyun-Taek
authors.initials: HT
authors.lastname: Kim
authors.forename: Anita
authors.initials: A
authors.lastname: Kulharya
authors.forename: Kyung-Soo
authors.initials: KS
authors.lastname: Ha
authors.forename: Yasuhide
authors.initials: Y
authors.lastname: Itokawa
authors.forename: Irene
authors.initials: I
authors.lastname: Meliciani
authors.forename: Wolfgang
authors.initials: W
authors.lastname: Wenzel
authors.forename: Deresa
authors.initials: D
authors.lastname: Lee
authors.forename: Georg
authors.initials: G
authors.lastname: Rosenberger
authors.forename: Metin
authors.initials: M
authors.lastname: Ozata
authors.forename: David P
authors.initials: DP
authors.lastname: Bick
authors.forename: Richard J
authors.initials: RJ
authors.lastname: Sherins
authors.forename: Takahiro
authors.initials: T
authors.lastname: Nagase
authors.forename: Mustafa
authors.initials: M
authors.lastname: Tekin
authors.forename: Soo-Hyun
authors.initials: SH
authors.lastname: Kim
authors.forename: Cheol-Hee
authors.initials: CH
authors.lastname: Kim
authors.forename: Hans-Hilger
authors.initials: HH
authors.lastname: Ropers
authors.forename: James F
authors.initials: JF
authors.lastname: Gusella
authors.forename: Vera
authors.initials: V
authors.lastname: Kalscheuer
authors.forename: Cheol Yong
authors.initials: CY
authors.lastname: Choi
authors.forename: Lawrence C
authors.initials: LC
authors.lastname: Layman
mesh_terms: D000293:Adolescent; D000818:Animals; D002879:Chromosomes, Human, Pair 10 / Q000235:genetics*; D018398:Homeodomain Proteins / Q000235:genetics*; D006801:Humans; D007006:Hypogonadism / Q000235:genetics*; D015151:Immunoblotting; D007150:Immunohistochemistry; D047468:Immunoprecipitation; D017403:In Situ Hybridization; D017404:In Situ Hybridization, Fluorescence; D017436:Kallmann Syndrome / Q000235:genetics*; D008297:Male; D008565:Membrane Proteins / Q000235:genetics* / Q000378:metabolism; D051379:Mice; D046228:Microarray Analysis; D020125:Mutation, Missense / Q000235:genetics; D020641:Polymorphism, Single Nucleotide / Q000235:genetics; D011518:Proto-Oncogene Proteins / Q000235:genetics* / Q000378:metabolism; D011627:Puberty / Q000235:genetics*; D051381:Rats; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014157:Transcription Factors / Q000235:genetics*; D014178:Translocation, Genetic / Q000235:genetics*; D020798:Two-Hybrid System Techniques; D015027:Zebrafish; D000099260:Empty Spiracles Homeobox Proteins; D000092468:Bromodomain Containing Proteins
chemical_list: D018398:Homeodomain Proteins; D008565:Membrane Proteins; D011518:Proto-Oncogene Proteins; D014157:Transcription Factors; D000099260:Empty Spiracles Homeobox Proteins; C435527:WDR11 protein, human; D000092468:Bromodomain Containing Proteins