The FKBP4 gene, encoding a regulator of the androgen receptor signaling pathway, is a novel candidate gene for androgen insensitivity syndrome
| Autor: | Kamila Kusz-Zamelczyk, Patrick Sproll, Erkut Ilaslan, Hasmik Hayrapetyan, Tamara Sarkisian, Renata Markosyan, Jadwiga Jaruzelska, Serge Nef, Brian Stevenson, Marcin Sajek, L. A. Livshits, Malgorzata Sajek |
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| Jazyk: | angličtina |
| Rok vydání: | 2020 |
| Předmět: |
Male
0301 basic medicine Candidate gene Androgen receptor signaling pathway Gene mutation Biology Catalysis lcsh:Chemistry Tacrolimus Binding Proteins Inorganic Chemistry disorder of sexual development (DSD) 03 medical and health sciences 0302 clinical medicine medicine Humans Exome Amino Acid Sequence Physical and Theoretical Chemistry Child Partial androgen insensitivity syndrome lcsh:QH301-705.5 Molecular Biology Gene Spectroscopy Exome sequencing Genetics partial androgen insensitivity syndrome (PAIS) 030219 obstetrics & reproductive medicine Communication Sexual Development Organic Chemistry General Medicine Androgen-Insensitivity Syndrome medicine.disease androgen insensitivity syndrome (AIS) Computer Science Applications Androgen receptor 030104 developmental biology lcsh:Biology (General) lcsh:QD1-999 FKBP4 Amino Acid Substitution Receptors Androgen Mutation Androgen insensitivity syndrome androgen receptor signaling Signal Transduction |
| Zdroj: | International Journal of Molecular Sciences International Journal of Molecular Sciences, Vol 21, Iss 8403, p 8403 (2020) |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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