Reversible kallmann syndrome, delayed puberty, and isolated anosmia occurring in a single family with a mutation in the fibroblast growth factor receptor 1 gene.
Details
Serval ID
serval:BIB_C1BA343BB5F2
Type
Article: article from journal or magazin.
Collection
Publications
Institution
Title
Reversible kallmann syndrome, delayed puberty, and isolated anosmia occurring in a single family with a mutation in the fibroblast growth factor receptor 1 gene.
Journal
Journal of Clinical Endocrinology and Metabolism
ISSN
0021-972X (Print)
ISSN-L
0021-972X
Publication state
Published
Issued date
2005
Peer-reviewed
Oui
Volume
90
Number
3
Pages
1317-1322
Language
english
Notes
Publication types: Journal Article ; Research Support, U.S. Gov't
Abstract
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. To date, the detailed reproductive phenotype of KS associated with mutations in the FGFR1 has yet to be described. We report a kindred comprising a male proband with KS and spontaneous reversibility, whose mother had delayed puberty and whose maternal grandfather isolated anosmia. The proband presented at age 18 yr with KS and was subsequently treated with testosterone (T) therapy. Upon discontinuation of T therapy, he recovered from his hypogonadotropic hypogonadism, as evidenced by a normal LH secretion pattern, sustained normal serum T levels, and active spermatogenesis. The three members of this single family harbor the same FGFR1 mutation (Arg(622)X) in the tyrosine kinase domain. This report demonstrates 1) the first genetic cause of the rare variant of reversible KS, 2) the reversal of hypogonadotropic hypogonadism in a proband carrying an FGFR1 mutation suggests a role of FGFR1 beyond embryonic GnRH neuron migration, and 3) a loss of function mutation in the FGFR1 gene causing delayed puberty.
Keywords
Adult, Amino Acid Sequence, Androgens/administration & dosage, Family Health, Gonadotropin-Releasing Hormone/metabolism, Humans, Hypothalamo-Hypophyseal System/physiology, Kallmann Syndrome/drug therapy, Kallmann Syndrome/genetics, Male, Molecular Sequence Data, Neurons/metabolism, Olfaction Disorders/genetics, Pedigree, Pituitary-Adrenal System/physiology, Puberty, Delayed/drug therapy, Puberty, Delayed/genetics, Receptor Protein-Tyrosine Kinases/genetics, Receptor, Fibroblast Growth Factor, Type 1, Receptors, Fibroblast Growth Factor/genetics, Testosterone/administration & dosage
Pubmed
Open Access
Yes
Create date
03/12/2014 15:41
Last modification date
20/08/2019 15:36