The FKBP4 Gene, Encoding a Regulator of the Androgen Receptor Signaling Pathway, Is a Novel Candidate Gene for Androgen Insensitivity Syndrome.
Détails
Etat: Public
Version: Final published version
Licence: CC BY 4.0
ID Serval
serval:BIB_1F7615E822AD
Type
Article: article d'un périodique ou d'un magazine.
Collection
Publications
Institution
Titre
The FKBP4 Gene, Encoding a Regulator of the Androgen Receptor Signaling Pathway, Is a Novel Candidate Gene for Androgen Insensitivity Syndrome.
Périodique
International journal of molecular sciences
ISSN
1422-0067 (Electronic)
ISSN-L
1422-0067
Statut éditorial
Publié
Date de publication
09/11/2020
Peer-reviewed
Oui
Volume
21
Numéro
21
Pages
8403
Langue
anglais
Notes
Publication types: Journal Article
Publication Status: epublish
Publication Status: epublish
Résumé
Androgen insensitivity syndrome (AIS), manifesting incomplete virilization in 46,XY individuals, is caused mostly by androgen receptor (AR) gene mutations. Therefore, a search for AR mutations is a routine approach in AIS diagnosis. However, some AIS patients lack AR mutations, which complicates the diagnosis. Here, we describe a patient suffering from partial androgen insensitivity syndrome (PAIS) and lacking AR mutations. The whole exome sequencing of the patient and his family members identified a heterozygous FKBP4 gene mutation, c.956T>C (p.Leu319Pro), inherited from the mother. The gene encodes FKBP prolyl isomerase 4, a positive regulator of the AR signaling pathway. This is the first report describing a FKBP4 gene mutation in association with a human disorder of sexual development (DSD). Importantly, the dysfunction of a homologous gene was previously reported in mice, resulting in a phenotype corresponding to PAIS. Moreover, the Leu319Pro amino acid substitution occurred in a highly conserved position of the FKBP4 region, responsible for interaction with other proteins that are crucial for the AR functional heterocomplex formation and therefore the substitution is predicted to cause the disease. We proposed the FKBP4 gene as a candidate AIS gene and suggest screening that gene for the molecular diagnosis of AIS patients lacking AR gene mutations.
Mots-clé
Amino Acid Sequence, Amino Acid Substitution/genetics, Androgen-Insensitivity Syndrome/genetics, Child, Exome/genetics, Humans, Male, Mutation/genetics, Receptors, Androgen/genetics, Sexual Development/genetics, Signal Transduction/genetics, Tacrolimus Binding Proteins/genetics, FKBP4, androgen insensitivity syndrome (AIS), androgen receptor signaling, disorder of sexual development (DSD), partial androgen insensitivity syndrome (PAIS)
Pubmed
Web of science
Open Access
Oui
Création de la notice
23/11/2020 16:16
Dernière modification de la notice
08/08/2024 7:30