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Communication

The FKBP4 Gene, Encoding a Regulator of the Androgen Receptor Signaling Pathway, Is a Novel Candidate Gene for Androgen Insensitivity Syndrome

1
Institute of Human Genetics, Polish Academy of Sciences, 60-479 Poznan, Poland
2
Endocrinology Department, “Muratsan” University Hospital, Endocrinology Clinic, Yerevan State Medical University, 0025 Yerevan, Armenia
3
Division of Endocrinology, University of Fribourg, 1700 Fribourg, Switzerland
4
SIB Swiss Institute of Bioinformatics, 1015 Lausanne, Switzerland
5
Department of Human Molecular Genetics, Institute of Molecular Biology and Biotechnology, Adam Mickiewicz University, 61-614 Poznan, Poland
6
Department of Medical Genetics, Yerevan State Medical University, 0025 Yerevan, Armenia
7
Center of Medical Genetics and Primary Health Care, 375010 Yerevan, Armenia
8
Institute of Molecular Biology and Genetics, National Academy of Sciences of Ukraine, 03143 Kyiv, Ukraine
9
Department of Genetic Medicine and Development, Faculty of Medicine, University of Geneva, CH-1211 Genève 4, Switzerland
*
Authors to whom correspondence should be addressed.
These authors contributed equally to this work.
Int. J. Mol. Sci. 2020, 21(21), 8403; https://doi.org/10.3390/ijms21218403
Received: 22 October 2020 / Revised: 2 November 2020 / Accepted: 4 November 2020 / Published: 9 November 2020
(This article belongs to the Special Issue Sex Determination Mechanisms and Disease)
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. View Full-Text
Keywords: androgen insensitivity syndrome (AIS); partial androgen insensitivity syndrome (PAIS); disorder of sexual development (DSD); androgen receptor signaling; FKBP4 androgen insensitivity syndrome (AIS); partial androgen insensitivity syndrome (PAIS); disorder of sexual development (DSD); androgen receptor signaling; FKBP4
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MDPI and ACS Style

Ilaslan, E.; Markosyan, R.; Sproll, P.; Stevenson, B.J.; Sajek, M.; Sajek, M.P.; Hayrapetyan, H.; Sarkisian, T.; Livshits, L.; Nef, S.; Jaruzelska, J.; Kusz-Zamelczyk, K. The FKBP4 Gene, Encoding a Regulator of the Androgen Receptor Signaling Pathway, Is a Novel Candidate Gene for Androgen Insensitivity Syndrome. Int. J. Mol. Sci. 2020, 21, 8403. https://doi.org/10.3390/ijms21218403

AMA Style

Ilaslan E, Markosyan R, Sproll P, Stevenson BJ, Sajek M, Sajek MP, Hayrapetyan H, Sarkisian T, Livshits L, Nef S, Jaruzelska J, Kusz-Zamelczyk K. The FKBP4 Gene, Encoding a Regulator of the Androgen Receptor Signaling Pathway, Is a Novel Candidate Gene for Androgen Insensitivity Syndrome. International Journal of Molecular Sciences. 2020; 21(21):8403. https://doi.org/10.3390/ijms21218403

Chicago/Turabian Style

Ilaslan, Erkut, Renata Markosyan, Patrick Sproll, Brian J. Stevenson, Malgorzata Sajek, Marcin P. Sajek, Hasmik Hayrapetyan, Tamara Sarkisian, Ludmila Livshits, Serge Nef, Jadwiga Jaruzelska, and Kamila Kusz-Zamelczyk. 2020. "The FKBP4 Gene, Encoding a Regulator of the Androgen Receptor Signaling Pathway, Is a Novel Candidate Gene for Androgen Insensitivity Syndrome" International Journal of Molecular Sciences 21, no. 21: 8403. https://doi.org/10.3390/ijms21218403

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