title: CCDC141 Mutation Identified in Anosmic Hypogonadotropic Hypogonadism (Kallmann Syndrome) Alters GnRH Neuronal Migration.
abstract: The first mutation in a gene associated with a neuronal migration disorder was identified in patients with Kallmann Syndrome, characterized by hypogonadotropic hypogonadism and anosmia. This pathophysiological association results from a defect in the development of the GnRH and the olfactory system. A recent genetic screening of Kallmann Syndrome patients revealed a novel mutation in CCDC141. Little is known about CCDC141, which encodes a coiled-coil domain containing protein. Here, we show that Ccdc141 is expressed in GnRH neurons and olfactory fibers and that knockdown of Ccdc141 reduces GnRH neuronal migration. Our findings in human patients and mouse models predict that CCDC141 takes part in embryonic migration of GnRH neurons enabling them to form a hypothalamic neuronal network to initiate pulsatile GnRH secretion and reproductive function.
authors.affiliation: National Institute of Neurological Disorders and Stroke (B.I.H., C.T.-B., P.J.C., J.D.R.T., S.W.), National Institutes of Health, Bethesda, Maryland 20892; Department of Biotechnology (L.D.K., A.K.T.), Institute of Sciences, Cukurova University, 01330 Adana, Turkey; Fırat University (Y.O.), 23119 Elazıg, Turkey; and Division of Pediatric Endocrinology (F.G., E.M., B.Y., A.K.T.), Faculty of Medicine, Cukurova University, 01330 Adana, Turkey.
authors.forename: B Ian
authors.initials: BI
authors.lastname: Hutchins
authors.affiliation: National Institute of Neurological Disorders and Stroke (B.I.H., C.T.-B., P.J.C., J.D.R.T., S.W.), National Institutes of Health, Bethesda, Maryland 20892; Department of Biotechnology (L.D.K., A.K.T.), Institute of Sciences, Cukurova University, 01330 Adana, Turkey; Fırat University (Y.O.), 23119 Elazıg, Turkey; and Division of Pediatric Endocrinology (F.G., E.M., B.Y., A.K.T.), Faculty of Medicine, Cukurova University, 01330 Adana, Turkey.
authors.forename: L Damla
authors.initials: LD
authors.lastname: Kotan
authors.affiliation: National Institute of Neurological Disorders and Stroke (B.I.H., C.T.-B., P.J.C., J.D.R.T., S.W.), National Institutes of Health, Bethesda, Maryland 20892; Department of Biotechnology (L.D.K., A.K.T.), Institute of Sciences, Cukurova University, 01330 Adana, Turkey; Fırat University (Y.O.), 23119 Elazıg, Turkey; and Division of Pediatric Endocrinology (F.G., E.M., B.Y., A.K.T.), Faculty of Medicine, Cukurova University, 01330 Adana, Turkey.
authors.forename: Carol
authors.initials: C
authors.lastname: Taylor-Burds
authors.affiliation: National Institute of Neurological Disorders and Stroke (B.I.H., C.T.-B., P.J.C., J.D.R.T., S.W.), National Institutes of Health, Bethesda, Maryland 20892; Department of Biotechnology (L.D.K., A.K.T.), Institute of Sciences, Cukurova University, 01330 Adana, Turkey; Fırat University (Y.O.), 23119 Elazıg, Turkey; and Division of Pediatric Endocrinology (F.G., E.M., B.Y., A.K.T.), Faculty of Medicine, Cukurova University, 01330 Adana, Turkey.
authors.forename: Yusuf
authors.initials: Y
authors.lastname: Ozkan
authors.affiliation: National Institute of Neurological Disorders and Stroke (B.I.H., C.T.-B., P.J.C., J.D.R.T., S.W.), National Institutes of Health, Bethesda, Maryland 20892; Department of Biotechnology (L.D.K., A.K.T.), Institute of Sciences, Cukurova University, 01330 Adana, Turkey; Fırat University (Y.O.), 23119 Elazıg, Turkey; and Division of Pediatric Endocrinology (F.G., E.M., B.Y., A.K.T.), Faculty of Medicine, Cukurova University, 01330 Adana, Turkey.
authors.forename: Paul J
authors.initials: PJ
authors.lastname: Cheng
authors.affiliation: National Institute of Neurological Disorders and Stroke (B.I.H., C.T.-B., P.J.C., J.D.R.T., S.W.), National Institutes of Health, Bethesda, Maryland 20892; Department of Biotechnology (L.D.K., A.K.T.), Institute of Sciences, Cukurova University, 01330 Adana, Turkey; Fırat University (Y.O.), 23119 Elazıg, Turkey; and Division of Pediatric Endocrinology (F.G., E.M., B.Y., A.K.T.), Faculty of Medicine, Cukurova University, 01330 Adana, Turkey.
authors.forename: Fatih
authors.initials: F
authors.lastname: Gurbuz
authors.affiliation: National Institute of Neurological Disorders and Stroke (B.I.H., C.T.-B., P.J.C., J.D.R.T., S.W.), National Institutes of Health, Bethesda, Maryland 20892; Department of Biotechnology (L.D.K., A.K.T.), Institute of Sciences, Cukurova University, 01330 Adana, Turkey; Fırat University (Y.O.), 23119 Elazıg, Turkey; and Division of Pediatric Endocrinology (F.G., E.M., B.Y., A.K.T.), Faculty of Medicine, Cukurova University, 01330 Adana, Turkey.
authors.forename: Jean D R
authors.initials: JD
authors.lastname: Tiong
authors.affiliation: National Institute of Neurological Disorders and Stroke (B.I.H., C.T.-B., P.J.C., J.D.R.T., S.W.), National Institutes of Health, Bethesda, Maryland 20892; Department of Biotechnology (L.D.K., A.K.T.), Institute of Sciences, Cukurova University, 01330 Adana, Turkey; Fırat University (Y.O.), 23119 Elazıg, Turkey; and Division of Pediatric Endocrinology (F.G., E.M., B.Y., A.K.T.), Faculty of Medicine, Cukurova University, 01330 Adana, Turkey.
authors.forename: Eda
authors.initials: E
authors.lastname: Mengen
authors.affiliation: National Institute of Neurological Disorders and Stroke (B.I.H., C.T.-B., P.J.C., J.D.R.T., S.W.), National Institutes of Health, Bethesda, Maryland 20892; Department of Biotechnology (L.D.K., A.K.T.), Institute of Sciences, Cukurova University, 01330 Adana, Turkey; Fırat University (Y.O.), 23119 Elazıg, Turkey; and Division of Pediatric Endocrinology (F.G., E.M., B.Y., A.K.T.), Faculty of Medicine, Cukurova University, 01330 Adana, Turkey.
authors.forename: Bilgin
authors.initials: B
authors.lastname: Yuksel
authors.affiliation: National Institute of Neurological Disorders and Stroke (B.I.H., C.T.-B., P.J.C., J.D.R.T., S.W.), National Institutes of Health, Bethesda, Maryland 20892; Department of Biotechnology (L.D.K., A.K.T.), Institute of Sciences, Cukurova University, 01330 Adana, Turkey; Fırat University (Y.O.), 23119 Elazıg, Turkey; and Division of Pediatric Endocrinology (F.G., E.M., B.Y., A.K.T.), Faculty of Medicine, Cukurova University, 01330 Adana, Turkey.
authors.forename: A Kemal
authors.initials: AK
authors.lastname: Topaloglu
authors.affiliation: National Institute of Neurological Disorders and Stroke (B.I.H., C.T.-B., P.J.C., J.D.R.T., S.W.), National Institutes of Health, Bethesda, Maryland 20892; Department of Biotechnology (L.D.K., A.K.T.), Institute of Sciences, Cukurova University, 01330 Adana, Turkey; Fırat University (Y.O.), 23119 Elazıg, Turkey; and Division of Pediatric Endocrinology (F.G., E.M., B.Y., A.K.T.), Faculty of Medicine, Cukurova University, 01330 Adana, Turkey.
authors.forename: Susan
authors.initials: S
authors.lastname: Wray
mesh_terms: D000818:Animals; D002465:Cell Movement / Q000235:genetics*; D007987:Gonadotropin-Releasing Hormone / Q000378:metabolism*; D006801:Humans; D017436:Kallmann Syndrome / Q000235:genetics*; D051379:Mice; D009154:Mutation; D009419:Nerve Tissue Proteins / Q000235:genetics* / Q000502:physiology; D009474:Neurons / Q000166:cytology / Q000378:metabolism*
chemical_list: C555242:CCDC141 protein, human; C555241:CCDC141 protein, mouse; D009419:Nerve Tissue Proteins; D007987:Gonadotropin-Releasing Hormone