The candidate gene for the X-linked Kallmann syndrome encodes a protein related to adhesion molecules

Legouis, Renaud; Hardelin, Jean‐Pierre; Levilliers, Jacqueline; Claverie, Jean‐Michel; Compain, Sylvie; Wunderle, Véronique M.; Millasseau, P; Paslier, Denis Le; Cohen, Daniel; Caterina, D; Bougueleret, Lydie; Waal, Henriette Delemarre-van de; Lutfalla, Georges; Weissenbach, Jean; Petit, Christine

doi:10.1016/0092-8674(91)90193-3

Cited by 646 publications

(346 citation statements)

References 76 publications

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“…110,111 Understanding of the molecular genetics of CHH and Kallmann syndrome has advanced tremendously in the past 20 years, since the first gene associated with Kallmann syndrome (KAL1 [ANOS1]) was identified by a positional cloning strategy in 1991 (Table 1). [112][113][114][115] KAL1 (ANOS1) encodes anosmin-1, a transiently expressed, locally restricted glycoprotein of embryonic extracellular matrices 116 that is involved in fibroblast growth factor (FGF) signalling. 117,118 To date, >25 different genes have been implicated in Kallmann syndrome and/or CHH, which accounts for ~50% of cases.…”

Section: Genetics Of Chhmentioning

confidence: 99%

European Consensus Statement on congenital hypogonadotropic hypogonadism—pathogenesis, diagnosis and treatment

et al. 2015

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| Congenital hypogonadotropic hypogonadism (CHH) is a rare disorder caused by the deficient production, secretion or action of gonadotropin-releasing hormone (GnRH), which is the master hormone regulating the reproductive axis. CHH is clinically and genetically heterogeneous, with >25 different causal genes identified to date. Clinically, the disorder is characterized by an absence of puberty and infertility. The association of CHH with a defective sense of smell (anosmia or hyposmia), which is found in ~50% of patients with CHH is termed Kallmann syndrome and results from incomplete embryonic migration of GnRHsynthesizing neurons. CHH can be challenging to diagnose, particularly when attempting to differentiate it from constitutional delay of puberty. A timely diagnosis and treatment to induce puberty can be beneficial for sexual, bone and metabolic health, and might help minimize some of the psychological effects of CHH. In most cases, fertility can be induced using specialized treatment regimens and several predictors of outcome have been identified. Patients typically require lifelong treatment, yet ~10-20% of patients exhibit a spontaneous recovery of reproductive function. This Consensus Statement summarizes approaches for the diagnosis and treatment of CHH and discusses important unanswered questions in the field.

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Section: Genetics Of Chhmentioning

confidence: 99%

European Consensus Statement on congenital hypogonadotropic hypogonadism—pathogenesis, diagnosis and treatment

et al. 2015

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“…Indeed, it has been known for a long time that a genetic defect in GnRH I secretion in rodents [6] and humans [7,8] results in a substantial decrease in serum gonadotropins associated with hypogonadism, impuberism and infertility. The same phenotype was observed more recently in patients with loss of function mutations in the GnRH type I receptor gene [9].…”

Section: Importance Of the Gnrh I System In Mammalsmentioning

confidence: 99%

Gonadotropin-releasing hormone and the control of gonadotrope function

et al. 2005

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-Normal gametogenesis and steroidogenesis is highly dependent on the pulsatile release of hypothalamic GnRH that binds high-affinity receptors present at the surface of pituitary gonadotrophs thereby triggering the synthesis and release of the gonadotropins LH and FSH. The mammalian GnRH receptor displays the classical heptahelical structure of G protein-coupled receptors with, however, a unique feature, the lack of a C-terminal tail. Accordingly, it does not desensitise sensu stricto, and internalises very poorly. It is now well established that GnRH stimulation induces the activation of a complex network of transduction pathways involved in the control of gonadotropin release and subunit gene expression. Other authors and ourselves have demonstrated that the GnRH action is associated with an increased complexity regarding gene regulation/cell function. Indeed GnRH affects the GnRH receptor gene itself and a number of additional genes that include some involved in cell signalling and auto-/paracrine regulation. The fact that GnRH regulates the expression of its own receptor, together with a host of other genes typically involved in its signal transduction cascades implies alteration/auto-adaptation in gonadotropic responsiveness. Furthermore, some of these genes respond differentially depending on whether the GnRH stimulation is intermittent or permanent suggesting specific roles in the dual process of activation/desensitisation. Thus, it can be assumed that the importance of pulsatility of GnRH action is closely related to, or dependent on, the inability of the GnRH receptor to desensitise. Moreover, multiple post-receptor events are crucial for both the regulation/plasticity of gonadotropic function and the maintenance of cell integrity.

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“…The gene underlying the X chromosome-linked form of Kallmann syndrome (KAL-1) was identified several years ago (Franco et al 1991;Legouis et al 1991).…”

Section: Introductionmentioning

confidence: 99%

Anosmin-1a is required for fasciculation and terminal targeting of olfactory sensory neuron axons in the zebrafish olfactory system

Yanicostas

Herbomel

Dipietromaria

et al. 2009

Molecular and Cellular Endocrinology

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1a is required for fasciculation and terminal targeting of olfactory sensory neuron axons in the zebrafish olfactory system. Molecular and Cellular Endocrinology, Elsevier, 2009, 312 (1-2) This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain.Page 1 Last, we showed that kal1a inactivation induced a severe decrease in the number of GABAergic and dopaminergic OB neurons. Though the phenotypes induced following anosmin-1a depletion in zebrafish embryos did not match precisely the defects observed in KS patients, our results provide the first demonstration of a direct requirement for anosmin-1 in OS development in vertebrates and stress the role of OB innervation on OB neuron differentiation.

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The candidate gene for the X-linked Kallmann syndrome encodes a protein related to adhesion molecules

Cited by 646 publications

References 76 publications

European Consensus Statement on congenital hypogonadotropic hypogonadism—pathogenesis, diagnosis and treatment

European Consensus Statement on congenital hypogonadotropic hypogonadism—pathogenesis, diagnosis and treatment

Gonadotropin-releasing hormone and the control of gonadotrope function

Anosmin-1a is required for fasciculation and terminal targeting of olfactory sensory neuron axons in the zebrafish olfactory system

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