kallmann syndrome

Summary

Summary: A genetically heterogeneous disorder caused by hypothalamic GNRH deficiency and OLFACTORY NERVE defects. It is characterized by congenital HYPOGONADOTROPIC HYPOGONADISM and ANOSMIA, possibly with additional midline defects. It can be transmitted as an X-linked (GENETIC DISEASES, X-LINKED), an autosomal dominant, or an autosomal recessive trait.

Top Publications

  1. Hardelin J. Kallmann syndrome: towards molecular pathogenesis. Mol Cell Endocrinol. 2001;179:75-81 pubmed
    ..link between GnRH-synthesising neurones and the embryonic olfactory system, thereby shedding new light on Kallmann syndrome, a developmental disease characterised by the association of hypogonadotropic hypogonadism and anosmia (or ..
  2. Ardouin O, Legouis R, Fasano L, David Watine B, Korn H, Hardelin J, et al. Characterization of the two zebrafish orthologues of the KAL-1 gene underlying X chromosome-linked Kallmann syndrome. Mech Dev. 2000;90:89-94 pubmed
    The gene underlying X chromosome-linked Kallmann syndrome, KAL-1, has been identified for several years, yet its role in development is still poorly understood...
  3. Okubo K, Sakai F, Lau E, Yoshizaki G, Takeuchi Y, Naruse K, et al. Forebrain gonadotropin-releasing hormone neuronal development: insights from transgenic medaka and the relevance to X-linked Kallmann syndrome. Endocrinology. 2006;147:1076-84 pubmed
    ..X-linked Kallmann syndrome (X-KS), characterized by failed gonadal function secondary to deficient gonadotropin secretion, is caused by ..
  4. Albuisson J, PĂȘcheux C, Carel J, Lacombe D, LeHeup B, Lapuzina P, et al. Kallmann syndrome: 14 novel mutations in KAL1 and FGFR1 (KAL2). Hum Mutat. 2005;25:98-9 pubmed
    b>Kallmann syndrome (KAL) combines hypogonadotropic hypogonadism and anosmia. Hypogonadism is due to Gonadotropin Releasing Hormone (GnRH) deficiency and anosmia is related to hypoplasia of the olfactory bulbs...
  5. Guioli S, Incerti B, Zanaria E, Bardoni B, Franco B, Taylor K, et al. Kallmann syndrome due to a translocation resulting in an X/Y fusion gene. Nat Genet. 1992;1:337-40 pubmed
    The X-linked Kallmann syndrome gene was recently cloned and homologous sequences of unknown functional significance identified on the Y chromosome...
  6. Monnier C, Dode C, Fabre L, Teixeira L, Labesse G, Pin J, et al. PROKR2 missense mutations associated with Kallmann syndrome impair receptor signalling activity. Hum Mol Genet. 2009;18:75-81 pubmed publisher
    b>Kallmann syndrome (KS) combines hypogonadism due to gonadotropin-releasing hormone deficiency, and anosmia or hyposmia, related to defective olfactory bulb morphogenesis...
  7. Soderlund D, Canto P, Mendez J. Identification of three novel mutations in the KAL1 gene in patients with Kallmann syndrome. J Clin Endocrinol Metab. 2002;87:2589-92 pubmed
  8. Hardelin J, Dode C. The complex genetics of Kallmann syndrome: KAL1, FGFR1, FGF8, PROKR2, PROK2, et al. Sex Dev. 2008;2:181-93 pubmed publisher
    b>Kallmann syndrome (KS) combines hypogonadotropic hypogonadism and anosmia. Anosmia is related to the absence or hypoplasia of the olfactory bulbs and tracts...
  9. Jongmans M, van Ravenswaaij Arts C, Pitteloud N, Ogata T, Sato N, Claahsen van der Grinten H, et al. CHD7 mutations in patients initially diagnosed with Kallmann syndrome--the clinical overlap with CHARGE syndrome. Clin Genet. 2009;75:65-71 pubmed publisher
    b>Kallmann syndrome (KS) is the combination of hypogonadotropic hypogonadism and anosmia or hyposmia, two features that are also frequently present in CHARGE syndrome. CHARGE syndrome is caused by mutations in the CHD7 gene...

More Information

Publications62

  1. Tornberg J, Sykiotis G, Keefe K, Plummer L, Hoang X, Hall J, et al. Heparan sulfate 6-O-sulfotransferase 1, a gene involved in extracellular sugar modifications, is mutated in patients with idiopathic hypogonadotrophic hypogonadism. Proc Natl Acad Sci U S A. 2011;108:11524-9 pubmed publisher
    ..These findings are consistent with a model in which KAL1 can act as a modulatory coligand with FGF to activate the FGF receptor in an HS-dependent manner...
  2. Rugarli E, Lutz B, Kuratani S, Wawersik S, Borsani G, Ballabio A, et al. Expression pattern of the Kallmann syndrome gene in the olfactory system suggests a role in neuronal targeting. Nat Genet. 1993;4:19-26 pubmed
    b>Kallmann syndrome is a genetic disorder characterized by a defect in olfactory system development, which appears to be due to an abnormality in the migration of olfactory axons and gonadotropin releasing hormone (Gn-RH) producing neurons...
  3. Hardelin J, Levilliers J, Blanchard S, Carel J, Leutenegger M, Pinard Bertelletto J, et al. Heterogeneity in the mutations responsible for X chromosome-linked Kallmann syndrome. Hum Mol Genet. 1993;2:373-7 pubmed
    b>Kallmann syndrome represents the association of hypogonadotropic hypogonadism with anosmia. Three modes of transmission, X chromosome-linked, autosomal recessive and autosomal dominant, have been described...
  4. Bhagavath B, Layman L. The genetics of hypogonadotropic hypogonadism. Semin Reprod Med. 2007;25:272-86 pubmed
    An up-to-date review of the genetic aspects of idiopathic hypogonadotropic hypogonadism (IHH)/Kallmann syndrome (KS) is presented...
  5. Dode C, Hardelin J. Clinical genetics of Kallmann syndrome. Ann Endocrinol (Paris). 2010;71:149-57 pubmed publisher
    The Kallmann syndrome (KS) combines hypogonadotropic hypogonadism (HH) with anosmia. This is a clinically and genetically heterogeneous disease...
  6. Teixeira L, Guimiot F, Dode C, Fallet Bianco C, Millar R, Delezoide A, et al. Defective migration of neuroendocrine GnRH cells in human arrhinencephalic conditions. J Clin Invest. 2010;120:3668-72 pubmed publisher
    Patients with Kallmann syndrome (KS) have hypogonadotropic hypogonadism caused by a deficiency of gonadotropin-releasing hormone (GnRH) and a defective sense of smell related to olfactory bulb aplasia...
  7. Koenigkam Santos M, Santos A, Versiani B, Diniz P, JĂșnior J, de Castro M. Quantitative magnetic resonance imaging evaluation of the olfactory system in Kallmann syndrome: correlation with a clinical smell test. Neuroendocrinology. 2011;94:209-17 pubmed publisher
    ..bulbs and sulci using dedicated magnetic resonance imaging (MRI) sequences and specific measurement tools in Kallmann syndrome (KS) patients with a well-established genotype and phenotype, as well as correlate MRI findings with a ..
  8. Hudson M, Kinnunen T, Cinar H, Chisholm A. C. elegans Kallmann syndrome protein KAL-1 interacts with syndecan and glypican to regulate neuronal cell migrations. Dev Biol. 2006;294:352-65 pubmed
    ..SDN-1 and GPN-1 are expressed in ventral neuroblasts and have redundant roles in KAL-1-dependent neuroblast migrations. Our findings suggest that KAL-1 interacts with multiple HSPGs to promote cell migration...
  9. Raivio T, Avbelj M, McCabe M, Romero C, Dwyer A, Tommiska J, et al. Genetic overlap in Kallmann syndrome, combined pituitary hormone deficiency, and septo-optic dysplasia. J Clin Endocrinol Metab. 2012;97:E694-9 pubmed publisher
    b>Kallmann syndrome (KS), combined pituitary hormone deficiency (CPHD), and septo-optic dysplasia (SOD) all result from development defects of the anterior midline in the human forebrain.
  10. Maione L, Benadjaoud S, Eloit C, Sinisi A, Colao A, Chanson P, et al. Computed tomography of the anterior skull base in Kallmann syndrome reveals specific ethmoid bone abnormalities associated with olfactory bulb defects. J Clin Endocrinol Metab. 2013;98:E537-46 pubmed publisher
    b>Kallmann syndrome (KS) is characterized by congenital hypogonadotropic hypogonadism (CHH) and an impaired sense of smell related to defective development of the olfactory system.
  11. Izumi Y, Tatsumi K, Okamoto S, Ogawa T, Hosokawa A, Matsuo T, et al. Analysis of the KAL1 gene in 19 Japanese patients with Kallmann syndrome. Endocr J. 2001;48:143-9 pubmed
    b>Kallmann syndrome is defined by the association of hypogonadotropic hypogonadism and anosmia. The KAL1 gene is responsible for the X-linked form of Kallmann syndrome...
  12. Sato N, Katsumata N, Kagami M, Hasegawa T, Hori N, Kawakita S, et al. Clinical assessment and mutation analysis of Kallmann syndrome 1 (KAL1) and fibroblast growth factor receptor 1 (FGFR1, or KAL2) in five families and 18 sporadic patients. J Clin Endocrinol Metab. 2004;89:1079-88 pubmed
    We report on the clinical and molecular findings in 25 males and three females with Kallmann syndrome (KS) aged 10-53 yr. Ten males were from five families, and the remaining 15 males and three females were apparently sporadic cases...
  13. Hasan K, Reddy S, Barsony N. Taste perception in kallmann syndrome, a model of congenital anosmia. Endocr Pract. 2007;13:716-20 pubmed
    To investigate taste, a component of flavor perception, using electrogustometry (EG) in patients with congenital anosmia associated with Kallmann syndrome (KS).
  14. Incerti B, Guioli S, Pragliola A, Zanaria E, Borsani G, Tonlorenzi R, et al. Kallmann syndrome gene on the X and Y chromosomes: implications for evolutionary divergence of human sex chromosomes. Nat Genet. 1992;2:311-4 pubmed
    The recently identified gene for X-linked Kallmann syndrome (hypogonadotropic hypogonadism and anosmia) has a closely related homologue on the Y chromosome...
  15. Kim H, Layman L. The role of CHD7 and the newly identified WDR11 gene in patients with idiopathic hypogonadotropic hypogonadism and Kallmann syndrome. Mol Cell Endocrinol. 2011;346:74-83 pubmed publisher
    ..anosmia and/or hypogonadism, features that overlap with idiopathic hypogonadotropic hypogonadism (IHH) and Kallmann syndrome (KS). Similarly, IHH/KS patients may also display partial CHARGE features...
  16. Laitinen E, Vaaralahti K, Tommiska J, Eklund E, Tervaniemi M, Valanne L, et al. Incidence, phenotypic features and molecular genetics of Kallmann syndrome in Finland. Orphanet J Rare Dis. 2011;6:41 pubmed publisher
    b>Kallmann syndrome (KS), comprised of congenital hypogonadotropic hypogonadism (HH) and anosmia, is a clinically and genetically heterogeneous disorder...
  17. Hu Y, Yu H, Shaw G, Pask A, Renfree M. Kallmann syndrome 1 gene is expressed in the marsupial gonad. Biol Reprod. 2011;84:595-603 pubmed publisher
    b>Kallmann syndrome is characterized by hypogonadotrophic hypogonadism and anosmia. The syndrome can be caused by mutations in several genes, but the X-linked form is caused by mutation in the Kallmann syndrome 1 (KAL1)...
  18. Bailleul Forestier I, Gros C, Zenaty D, Bennaceur S, Leger J, de Roux N. Dental agenesis in Kallmann syndrome individuals with FGFR1 mutations. Int J Paediatr Dent. 2010;20:305-12 pubmed publisher
    b>Kallmann syndrome (KS) is a rare genetic disorder characterised by central hypogonadism with a lack of sense of smell and in some cases renal aplasia, deafness, syndactyly, cleft lip/palate, and dental agenesis...
  19. Dode C, Hardelin J. Kallmann syndrome. Eur J Hum Genet. 2009;17:139-46 pubmed publisher
    The Kallmann syndrome (KS) combines hypogonadotropic hypogonadism (HH) with anosmia. This is a clinically and genetically heterogeneous disease...
  20. Sinisi A, Asci R, Bellastella G, Maione L, Esposito D, Elefante A, et al. Homozygous mutation in the prokineticin-receptor2 gene (Val274Asp) presenting as reversible Kallmann syndrome and persistent oligozoospermia: case report. Hum Reprod. 2008;23:2380-4 pubmed publisher
    Prokineticin 2 (Prok2) or prokineticin-receptor2 (Prok-R2) gene mutations are associated with Kallmann syndrome (KS). We describe a new homozygous mutation of Prok-R2 gene in a man displaying KS with an apparent reversal of hypogonadism...
  21. Raivio T, Falardeau J, Dwyer A, Quinton R, Hayes F, Hughes V, et al. Reversal of idiopathic hypogonadotropic hypogonadism. N Engl J Med. 2007;357:863-73 pubmed
    Idiopathic hypogonadotropic hypogonadism, which may be associated with anosmia (the Kallmann syndrome) or with a normal sense of smell, is a treatable form of male infertility caused by a congenital defect in the secretion or action of ..
  22. Leroy C, Fouveaut C, Leclercq S, Jacquemont S, Boullay H, Lespinasse J, et al. Biallelic mutations in the prokineticin-2 gene in two sporadic cases of Kallmann syndrome. Eur J Hum Genet. 2008;16:865-8 pubmed publisher
    b>Kallmann syndrome is a developmental disease that combines hypogonadotropic hypogonadism and anosmia...
  23. Karges B, de Roux N. Molecular genetics of isolated hypogonadotropic hypogonadism and Kallmann syndrome. Endocr Dev. 2005;8:67-80 pubmed
    ..IHH associated with impaired olfactory function (Kallmann syndrome) may be caused by mutations of the X-chromosomal KAL1 (encoding anosmin) or the fibroblast growth factor ..
  24. Pedersen White J, Chorich L, Bick D, Sherins R, Layman L. The prevalence of intragenic deletions in patients with idiopathic hypogonadotropic hypogonadism and Kallmann syndrome. Mol Hum Reprod. 2008;14:367-70 pubmed publisher
    Idiopathic hypogonadotropic hypogonadism (IHH) and Kallmann syndrome (KS) are clinically and genetically heterogeneous disorders caused by a deficiency of gonadotrophin-releasing hormone (GnRH)...
  25. Massin N, Pecheux C, Eloit C, Bensimon J, Galey J, Kuttenn F, et al. X chromosome-linked Kallmann syndrome: clinical heterogeneity in three siblings carrying an intragenic deletion of the KAL-1 gene. J Clin Endocrinol Metab. 2003;88:2003-8 pubmed
    b>Kallmann syndrome (KS) is characterized by the association of hypogonadotropic hypogonadism and anosmia. The gene underlying the X chromosome-linked form of the disease, KAL-1, consists of 14 coding exons...
  26. Quinton R, Cheow H, Tymms D, Bouloux P, Wu F, Jacobs H. Kallmann's syndrome: is it always for life?. Clin Endocrinol (Oxf). 1999;50:481-5 pubmed
    ..We present evidence for the existence of a variant form of KS, in which endogenous gonadotrophin secretion recovers spontaneously in later life...
  27. Hanchate N, Giacobini P, Lhuillier P, Parkash J, Espy C, Fouveaut C, et al. SEMA3A, a gene involved in axonal pathfinding, is mutated in patients with Kallmann syndrome. PLoS Genet. 2012;8:e1002896 pubmed publisher
    b>Kallmann syndrome (KS) associates congenital hypogonadism due to gonadotropin-releasing hormone (GnRH) deficiency and anosmia. The genetics of KS involves various modes of transmission, including oligogenic inheritance...
  28. Jarzabek K, Wolczynski S, Lesniewicz R, Plessis G, Kottler M. Evidence that FGFR1 loss-of-function mutations may cause variable skeletal malformations in patients with Kallmann syndrome. Adv Med Sci. 2012;57:314-21 pubmed publisher
    Loss-of-function mutations in FGFR1 have been identified in approximately 10% of the Kallmann syndrome (KS) patients...
  29. Pitteloud N, Meysing A, Quinton R, Acierno J, Dwyer A, Plummer L, et al. Mutations in fibroblast growth factor receptor 1 cause Kallmann syndrome with a wide spectrum of reproductive phenotypes. Mol Cell Endocrinol. 2006;254-255:60-9 pubmed
  30. Madan R, Sawlani V, Gupta S, Phadke R. MRI findings in Kallmann syndrome. Neurol India. 2004;52:501-3 pubmed
    b>Kallmann syndrome (KS) is a neuronal migration disorder characterised by hypogonadotrophic hypogonadism and anosmia or hyposmia. Five patients with clinical findings suggestive of KS were evaluated with MRI...
  31. Tsai P, Gill J. Mechanisms of disease: Insights into X-linked and autosomal-dominant Kallmann syndrome. Nat Clin Pract Endocrinol Metab. 2006;2:160-71 pubmed
    b>Kallmann syndrome (KS) is a disorder characterized by hypogonadotropic hypogonadism and anosmia. Although KS is genetically heterogeneous, only two causal genes have been identified to date...
  32. Ribeiro R, Vieira T, Abucham J. Reversible Kallmann syndrome: report of the first case with a KAL1 mutation and literature review. Eur J Endocrinol. 2007;156:285-90 pubmed
    b>Kallmann syndrome (KS) describes the association of isolated hypogonadotropic hypogonadism with hypo/anosmia. A few KS patients may reverse hypogonadism after testosterone withdrawal, a variant known as reversible KS...
  33. Pitteloud N, Quinton R, Pearce S, Raivio T, Acierno J, Dwyer A, et al. Digenic mutations account for variable phenotypes in idiopathic hypogonadotropic hypogonadism. J Clin Invest. 2007;117:457-63 pubmed
    ..To address this issue, we studied 2 families, one with Kallmann syndrome (IHH and anosmia) and another with normosmic IHH, in which a single-gene defect had been identified: a ..
  34. Kaplan J, Bernstein J, Kwan A, Hudgins L. Clues to an early diagnosis of Kallmann syndrome. Am J Med Genet A. 2010;152A:2796-801 pubmed publisher
    b>Kallmann syndrome (KS) is defined by the association of idiopathic hypogonadotropic hypogonadism and anosmia/hyposmia...
  35. Hardelin J, Julliard A, Moniot B, Soussi Yanicostas N, Verney C, Schwanzel Fukuda M, et al. Anosmin-1 is a regionally restricted component of basement membranes and interstitial matrices during organogenesis: implications for the developmental anomalies of X chromosome-linked Kallmann syndrome. Dev Dyn. 1999;215:26-44 pubmed
    b>Kallmann syndrome is a developmental disease characterized by gonadotropin-releasing hormone (GnRH) deficiency and olfactory bulb hypoplasia...
  36. Rugarli E, Ghezzi C, Valsecchi V, Ballabio A. The Kallmann syndrome gene product expressed in COS cells is cleaved on the cell surface to yield a diffusible component. Hum Mol Genet. 1996;5:1109-15 pubmed
    b>Kallmann syndrome is characterized by hypogonadotropic hypogonadism and anosmia and caused by a defect of migration and targeting of gonadotropin-releasing hormone-secreting neurons and olfactory axons during embryonic development...
  37. Matsumoto S, Yamazaki C, Masumoto K, Nagano M, Naito M, Soga T, et al. Abnormal development of the olfactory bulb and reproductive system in mice lacking prokineticin receptor PKR2. Proc Natl Acad Sci U S A. 2006;103:4140-5 pubmed
    ..The phenotype of the Pkr2(-/-) mice showed similarity to the clinical features of Kallmann syndrome, a human disease characterized by association of hypogonadotropic hypogonadism and anosmia...
  38. Soussi Yanicostas N, De Castro F, Julliard A, Perfettini I, Chedotal A, Petit C. Anosmin-1, defective in the X-linked form of Kallmann syndrome, promotes axonal branch formation from olfactory bulb output neurons. Cell. 2002;109:217-28 pubmed
    The physiological role of anosmin-1, defective in the X chromosome-linked form of Kallmann syndrome, is not yet known...
  39. Canto P, Munguia P, Soderlund D, Castro J, Mendez J. Genetic analysis in patients with Kallmann syndrome: coexistence of mutations in prokineticin receptor 2 and KAL1. J Androl. 2009;30:41-5 pubmed publisher
    b>Kallmann syndrome (KS) is characterized by the association of hypogonadotropic hypogonadism and anosmia or hyposmia...
  40. Falardeau J, Chung W, Beenken A, Raivio T, Plummer L, Sidis Y, et al. Decreased FGF8 signaling causes deficiency of gonadotropin-releasing hormone in humans and mice. J Clin Invest. 2008;118:2822-31 pubmed publisher
    Idiopathic hypogonadotropic hypogonadism (IHH) with anosmia (Kallmann syndrome; KS) or with a normal sense of smell (normosmic IHH; nIHH) are heterogeneous genetic disorders associated with deficiency of gonadotropin-releasing hormone (..
  41. Pitteloud N, Zhang C, Pignatelli D, Li J, Raivio T, Cole L, et al. Loss-of-function mutation in the prokineticin 2 gene causes Kallmann syndrome and normosmic idiopathic hypogonadotropic hypogonadism. Proc Natl Acad Sci U S A. 2007;104:17447-52 pubmed
    ..in the human presents either as normosmic idiopathic hypogonadotropic hypogonadism (nIHH) or with anosmia [Kallmann syndrome (KS)]...
  42. Trarbach E, Costa E, Versiani B, de Castro M, Baptista M, Garmes H, et al. Novel fibroblast growth factor receptor 1 mutations in patients with congenital hypogonadotropic hypogonadism with and without anosmia. J Clin Endocrinol Metab. 2006;91:4006-12 pubmed
    b>Kallmann syndrome is a clinically and genetically heterogeneous disorder...
  43. de Roux N. Isolated gonadotropic deficiency with and without anosmia: a developmental defect or a neuroendocrine regulation abnormality of the gonadotropic axis. Horm Res. 2005;64 Suppl 2:48-55 pubmed
    ..hypogonadotropic hypogonadism is classified into two categories: one that is associated with anosmia (Kallmann syndrome) and one that is apparently isolated...
  44. Dode C, Hardelin J. Kallmann syndrome: fibroblast growth factor signaling insufficiency?. J Mol Med (Berl). 2004;82:725-34 pubmed
    b>Kallmann syndrome (KAL) is a developmental disease that combines hypogonadotropic hypogonadism and anosmia. Anosmia is related to the absence or hypoplasia of the olfactory bulbs...
  45. del Castillo I, Cohen Salmon M, Blanchard S, Lutfalla G, Petit C. Structure of the X-linked Kallmann syndrome gene and its homologous pseudogene on the Y chromosome. Nat Genet. 1992;2:305-10 pubmed
    The gene for the X-linked Kallmann syndrome (KAL), a developmental disorder characterized by hypogonadotropic hypogonadism and anosmia, maps to Xp22.3 and has a homologous locus, KALP, on Yq11...
  46. Sykiotis G, Plummer L, Hughes V, Au M, Durrani S, Nayak Young S, et al. Oligogenic basis of isolated gonadotropin-releasing hormone deficiency. Proc Natl Acad Sci U S A. 2010;107:15140-4 pubmed publisher
  47. Kim H, Bhagavath B, Layman L. Clinical manifestations of impaired GnRH neuron development and function. Neurosignals. 2008;16:165-82 pubmed publisher
    ..and disruption of this process causes idiopathic hypogonadotropic hypogonadism (IHH) with anosmia (Kallmann syndrome (KS))...
  48. Cole L, Sidis Y, Zhang C, Quinton R, Plummer L, Pignatelli D, et al. Mutations in prokineticin 2 and prokineticin receptor 2 genes in human gonadotrophin-releasing hormone deficiency: molecular genetics and clinical spectrum. J Clin Endocrinol Metab. 2008;93:3551-9 pubmed publisher
    ..Mice deficient in prokineticin 2(PROK2) and prokineticin receptor2 (PROKR2) exhibit variable olfactory bulb dysgenesis and GnRH neuronal migration defects reminiscent of human GnRH deficiency...
  49. Colquhoun Kerr J, Gu W, Jameson J, Withers S, Bode H. X-linked Kallmann syndrome and renal agenesis occurring together and independently in a large Australian family. Am J Med Genet. 1999;83:23-7 pubmed
    Males with X-linked Kallmann syndrome (XLKS) may have renal agenesis. We studied a large kindred with a history of eight males affected by XLKS born in five generations...
  50. Dode C, Fouveaut C, Mortier G, Janssens S, Bertherat J, Mahoudeau J, et al. Novel FGFR1 sequence variants in Kallmann syndrome, and genetic evidence that the FGFR1c isoform is required in olfactory bulb and palate morphogenesis. Hum Mutat. 2007;28:97-8 pubmed
    In a new cohort of 141 unrelated patients affected by Kallmann syndrome we identified FGFR1 sequence variants in 17 patients, all in the heterozygous state. The fifteen novel variants consist of 10 missense (p.N77K, p.C101F, p.R250W, p...
  51. Pitteloud N, Acierno J, Meysing A, Dwyer A, Hayes F, Crowley W. Reversible kallmann syndrome, delayed puberty, and isolated anosmia occurring in a single family with a mutation in the fibroblast growth factor receptor 1 gene. J Clin Endocrinol Metab. 2005;90:1317-22 pubmed
    b>Kallmann syndrome (KS) is a clinically and genetically heterogeneous disorder. Recently, loss-of-function mutations in the fibroblast growth factor receptor 1 (FGFR1) gene have been shown to cause autosomal dominant KS...
  52. Abreu A, Trarbach E, de Castro M, Frade Costa E, Versiani B, Matias Baptista M, et al. Loss-of-function mutations in the genes encoding prokineticin-2 or prokineticin receptor-2 cause autosomal recessive Kallmann syndrome. J Clin Endocrinol Metab. 2008;93:4113-8 pubmed publisher
    ..Physiological activation of the prokineticin pathway has a critical role in olfactory bulb morphogenesis and GnRH secretion in mice...
  53. Kim S, Hu Y, Cadman S, Bouloux P. Diversity in fibroblast growth factor receptor 1 regulation: learning from the investigation of Kallmann syndrome. J Neuroendocrinol. 2008;20:141-63 pubmed
    The unravelling of the genetic basis of the hypogonadotrophic hypogonadal disorders, including Kallmann syndrome (KS), has led to renewed interest into the developmental biology of gonadotrophin-releasing hormone (GnRH) neurones and, ..