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Paediatric phenotype of Kallmann syndrome due to mutations of fibroblast growth factor receptor 1 (FGFR1).

Authors:
Delphine Zenaty Patricia Bretones Cécile Lambe Isabelle Guemas Michel David Juliane Léger Nicolas de Roux

Mol Cell Endocrinol 2006 Jul 6;254-255:78-83. Epub 2006 Jun 6.

Assistance Publique Hôpitaux de Paris, Robert Debre Hospital Paediatric Endocrinology unit, Robert Debré Hospital, Paris, France.

Kallmann syndrome characterised by hypogonadotropic hypogonadism (HH) and anosmia is genetically heterogeneous with X-linked, autosomal dominant and autosomal recessive forms. The autosomal dominant form due to loss of function mutation in the fibroblast growth factor receptor 1 (FGFR1) accounts for about 10% of cases. We report here three paediatric cases of Kallmann syndrome with unusual phenotype in two unrelated patients with severe ear anomalies (hypoplasia or agenesis of external ear) associated with classical features, such as cleft palate, dental agenesis, syndactylia, micropenis and cryptorchidism. We found de novo mutation in these two patients (Cys178Ser and Arg622Gly, respectively), and one inherited Arg622Gln mutation with intrafamilial variable phenotype. These genotype-phenotype correlations indicate that paediatric phenotypic expression of FGFR1 loss of function mutations is highly variable, the severity of the oro-facial malformations at birth does not predict gonadotropic function at the puberty and that de novo mutations of FGFR1 are relatively frequent.

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http://dx.doi.org/10.1016/j.mce.2006.04.006DOI Listing
July 2006

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Int J Mol Sci 2021 Feb 21;22(4). Epub 2021 Feb 21.

Institute of Cancer Research, Department of Medicine I, Comprehensive Cancer Center, Medical University of Vienna, A-1090 Vienna, Austria.

Kallmann syndrome is the result of innate genetic defects in the fibroblast growth factor (FGF) regulated signaling network causing diminished signal transduction. One of the rare mutations associated with the syndrome alters the Sprouty (Spry)4 protein by converting the serine at position 241 into a tyrosine. In this study, we characterize the tyrosine Spry4 mutant protein in the primary human embryonic lung fibroblasts WI-38 and osteosarcoma-derived cell line U2OS. Read More

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Front Endocrinol (Lausanne) 2020 1;11:592831. Epub 2021 Feb 1.

Liaoning Provincial Key Laboratory of Endocrine Diseases, Department of Endocrinology and Metabolism, Institute of Endocrinology, The First Hospital, China Medical University, Shenyang, China.

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Clin Endocrinol (Oxf) 2021 Feb 6. Epub 2021 Feb 6.

NHC key laboratory of Endocrinology, Peking Union Medical College Hospital), Department of Endocrinology, Union Medical College Hospital, Chinese Academy of Medical Sciences, Beijing, 100730, China.

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Genet Med 2021 Jan 25. Epub 2021 Jan 25.

Department of Pediatrics, Division of Pediatric Endocrinology, University of Mississippi Medical Center, Jackson, MS, USA.

Purpose: Idiopathic hypogonadotropic hypogonadism (IHH) is characterized by absent puberty and subsequent infertility due to gonadotropin-releasing hormone (GnRH) deficiency. IHH can be accompanied by normal or compromised olfaction (Kallmann syndrome). Several semaphorins are known potent modulators of GnRH, olfactory, and vomeronasal system development. Read More

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Harvard Reproductive Sciences Center, The Reproductive Endocrine Unit and The Endocrine Unit of the Department of Medicine, Massachusetts General Hospital, Boston, MA, USA.

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