Abstract
Androgen insensitivity syndrome (AIS) occurs when target tissues are resistant to the effect of androgens resulting in phenotype with varying degrees of feminization ranging from male infertility to completely normal female external genitalia in patients with male karyotype. Androgen receptor (AR) following activation by androgenic hormones binds to DNA in cells of target tissues and induces biological changes leading to differentiation and development of male urogenital structures. To date, more than 800 mutations in AR gene have been described in patients with AIS with the majority being located in the ligand-binding domain. Here a detailed description of a family with two affected 46,XY females with complete androgen insensitivity is provided. Whole exome sequencing revealed a novel mutation in exon 1 (c.238C>T) of AR gene. The mutation was detected in a proband and her sister, both with normal male karyotype and phenotypic expression of complete androgen insensitivity syndrome.
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References
Brinkmann, A.O., Molecular basis of androgen insensitivity, Mol. Cell. Endocrinol., 2011, vol. 179, nos. 1–2, pp. 105–109.
Tan, M.H., Li, J., Xu, H.E., Melcher, K., Yong, E.L., Androgen receptor: structure, role in prostate cancer and drug discovery, Acta. Pharmacol. Sin., 2015, vol. 36, no. 1, pp. 3–23.
Trapman, J., Klaassen, P., Kuiper, G.G., van der Korput, J.A., Faber, P.W. et al., Cloning, structure and expression of a cDNA encoding the human androgen receptor, Biochem. Biophys. Res. Commun., 1988, vol. 153, no. 1, pp. 241–248.
Jaaskelainen J., Molecular biology of androgen insensitivity, Mol. Cell. Endocrinol., 2012, vol. 352, nos. 1–2, pp. 4–12.
Gottlieb, B., Beitel, L.K., Nadarajah, A., Palioura, M., Trifiro, M. The Androgen Receptor Gene Mutations Database (ARDB), Upd. Hum. Mut., 2012, vol. 33, no. 6, pp. 887–894.
Radpour, R., Falah, M., Aslani, A., Zhong, X.Y., Saleki, A., Identification of a critical novel mutation in the exon 1 of androgen receptor gene in 2 brothers with complete androgen insensitivity syndrome, J. Androl., 2009, vol. 30, no. 3, pp. 230–232.
Bain, D.L., Heneghan, A.F., Connaghan-Jones, K.D., Miura, M.T., Nuclear receptor structure: Implications for function, Ann. Rev. Physiol., 2007, vol. 69, no. 1, pp. 201–220.
Liao, G., Chen, L.Y., Zhang, A., Godavarthy, A., Xia, F., et al., Regulation of androgen receptor activity by nuclear receptor corepressor SMRT, J. Biol. Chem., 2003, vol. 278, no. 7, pp. 5052–5061.
Shao, J., Hou, J., Li, B., Li, D., Zhang, N. et al., Different types of androgen receptor mutations in patients with complete androgen insensitivity syndrome, Intract. Rar. Dis. Res., 2015, vol. 4, no. 1, pp. 54–59.
Galani, A., Kitsiou-Tzeli S., Sofokleous, C., Kanavakis, E., Kaplini-Mavrou, A. Androgene insensitivity syndrome: clinical features and molecular defects, Horm., 2008, vol. 7, no. 3, pp. 217–229.
Schwarz, J.M., Cooper, D.N., Schuelke, M., Seelow, D. MutationTaster2: mutation prediction for the deepsequencing age, Nat. Methods., 2014, vol. 11, no. 4, pp. 361–362.
Clarke, L., Zheng-Bradley, X., Smith, R., Kulesha, E., Xiao, C. et al., 1000 Genomes Project Consortium. The 1000 Genomes Project: data management and community access, Nat. Methods., 2012, vol. 27, no. 5, pp. 459–462.
Stenson, P.D., Ball, E.V., Mort, M., Philips, A.D., Shaw, K. et al., The Human Gene Mutation Database (HGMD) and its exploitation in the fields of personalized genomics and molecular evolution, Curr. Protoc. Bioinformatics, 2012, Chapter 1, Unit 1.13.
Zoppi, S., Wilson, C.M., Harbison, M.D., Griffin, J.E., Willson, J.D. et al., Complete testicular feminization caused by amino-terminal truncation of the androgen receptor with downstream initiation, J. Clin. Invest., 1993, vol. 91, no. 3, pp. 1105–1112.
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Original Russian Text © L.Y. Pylyp, D.O. Mykytenko, I.O. Sudoma, V.D. Zukin, 2017, published in Tsitologiya i Genetika, 2017, Vol. 51, No. 4, pp. 39–43.
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Pylyp, L.Y., Mykytenko, D.O., Sudoma, I.O. et al. A novel androgen receptor mutation in a patient with complete androgen insensitivity syndrome. Cytol. Genet. 51, 268–271 (2017). https://doi.org/10.3103/S0095452717040089
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DOI: https://doi.org/10.3103/S0095452717040089