A clinical case of partial androgen resistance syndrome (Reifenstein syndrome)

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Abstract

In the paper we describe a clinical case and provide integrated clinical and laboratory data of a  patient with partial androgen resistance syndrome. A 25-year-old male was referred for medical evaluation for an infertile marriage. After a  comprehensive assessment, he was diagnosed with hypergonadotropic hypogonadism, coronal hypospadia, left-sided varicocele, and oligoasthenoteratozoospermia. Cytogenetic analysis showed normal male karyotype (46,XY). Molecular genetic analysis identified the c.731_736delCGGTGT mutation in the exon 1 of the androgen receptor (AR) gene, what allowed for making a diagnosis of Reifenstein syndrome. In addition, we give a brief literature review of the clinical conditions associated with abnormal androgen sensitivity and discuss the problems of testing and counseling of patients with partial androgen resistance syndrome.

About the authors

L. K. Dzeranova

Endocrinology Research Center

Author for correspondence.
Email: dzeranovalk@yandex.ru
ORCID iD: 0000-0002-0327-4619

Larisa K. Dzeranova – MD, PhD, Academic Secretary, Chief Research Fellow, Department of Neuroendocrinology and Osteopathy; Professor, Chair of Endocrinology, Institute of Higher and Continuing Professional Education 

11 Dmitriya Ul'yanova ul., Moscow, 117036

Russian Federation

E. A. Pigarova

Endocrinology Research Center

Email: kpigarova@gmail.com
ORCID iD: 0000-0001-6539-466X

Ekaterina A. Pigarova – Acting Director, Institute of Higher and Continuing Professional Education 

11 Dmitriya Ul'yanova ul., Moscow, 117036

Russian Federation

E. V. Ivannikova

Endocrinology Research Center

Email: fake@neicon.ru
ORCID iD: 0000-0002-2764-1049

Ekaterina V. Ivannikova – MD, PhD, Senior Research Fellow, Department of Obesity and Pathology of Metabolism, Unit of Therapeutic Endocrinology 

11 Dmitriya Ul'yanova ul., Moscow, 117036

Russian Federation

L. F. Kurilo

Research Centre of Medical Genetics

Email: fake@neicon.ru

Lyubov' F. Kurilo – Chief Research Fellow, Laboratory of Genetics of Reproduction Disorders 

1 Moskvorech'e ul., Moscow, 115522

Russian Federation

V. B. Chernykh

Research Centre of Medical Genetics

Email: fake@neicon.ru
ORCID iD: 0000-0002-7615-8512

Vyacheslav B. Chernykh – Head of Laboratory of Genetics of Reproduction Disorders 

1 Moskvorech'e ul., Moscow, 115522

Russian Federation

A. V. Polyakov

Research Centre of Medical Genetics

Email: fake@neicon.ru

Aleksandr V. Polyakov – Head of Laboratory of DNA diagnostics 

1 Moskvorech'e ul., Moscow, 115522

Russian Federation

References

  1. Hashmi A, Hanif F, Hanif SM, Abdullah FE, Shamim MS. Complete Androgen Insensitivity Syndrome. J Coll Physicians Surg Pak. 2008;18(7):442–4.
  2. Giwercman A, Kledal T, Schwartz M, Giwercman YL, Leffers H, Zazzi H, Wedell A, Skakkebaek NE. Preserved male fertility despite decreased androgen sensitivity caused by a mutation in the ligand-binding domain of the androgen receptor gene. J Clin Endocrinol Metab. 2000;85(6):2253–9. doi: 10.1210/jcem.85.6.6626.
  3. Trzmiel-Bira A, Filus A, Kuliczkowska-Płaksej J, Laczmański L, Medraś M. [The androgen receptor gene polymorphism and clinical picture of androgen deficiency syndrome during aging male of men's population in Wroclaw]. Endokrynol Pol. 2009;60(5):370–8. Polish.
  4. Jääskeläinen J. Molecular biology of androgen insensitivity. Mol Cell Endocrinol. 2012;352(1– 2):4–12. doi: 10.1016/j.mce.2011.08.006.
  5. Колодкина АА, Калинченко НЮ, Нижник АН, Файзулин АК, Карманов МЕ, Тюльпаков АН. Дефекты генов AR и SRD5A2 у пациентов с нарушением периферического действия андрогенов. Проблемы эндокринологии. 2011;57(5):24–9. doi: 10.14341/probl201157524-29.
  6. Ahmed SF, Cheng A, Dovey L, Hawkins JR, Martin H, Rowland J, Shimura N, Tait AD, Hughes IA. Phenotypic features, androgen receptor binding, and mutational analysis in 278 clinical cases reported as androgen insensitivity syndrome. J Clin Endocrinol Metab. 2000;85(2): 658–65. doi: 10.1210/jcem.85.2.6337.
  7. Audi L, Fernández-Cancio M, Carrascosa A, Andaluz P, Torán N, Piró C, Vilaró E, Vicens-Calvet E, Gussinyé M, Albisu MA, Yeste D, Clemente M, Hernández de la Calle I, Del Campo M, Vendrell T, Blanco A, Martínez-Mora J, Granada ML, Salinas I, Forn J, Calaf J, Angerri O, Martínez-Sopena MJ, Del Valle J, García E, Gracia-Bouthelier R, Lapunzina P, Mayayo E, Labarta JI, Lledó G, Sánchez Del Pozo J, Arroyo J, Pérez-Aytes A, Beneyto M, Segura A, Borrás V, Gabau E, Caimarí M, Rodríguez A, Martínez-Aedo MJ, Carrera M, Castaño L, Andrade M, Bermúdez de la Vega JA; Grupo de Apoyo al Síndrome de Insensibilidad a los Andrógenos (GrApSIA). Novel (60%) and recurrent (40%) androgen receptor gene mutations in a series of 59 patients with a 46,XY disorder of sex development. J Clin Endocrinol Metab. 2010;95(4): 1876–88. doi: 10.1210/jc.2009-2146.
  8. Coutant R, Mallet D, Lahlou N, Bouhours-Nouet N, Guichet A, Coupris L, Croué A, Morel Y. Heterozygous mutation of steroidogenic factor-1 in 46,XY subjects may mimic partial androgen insensitivity syndrome. J Clin Endocrinol Metab. 2007;92(8):2868–73. doi: 10.1210/jc.2007-0024.
  9. Grumbach MM, Hughes IA, Conte FA. Disorders of sex differentiation. In: Melmed S, Polonsky K, P. PR, Kronenberg H, eds. Williams Textbook of Endocrinology. 12th ed. Philadelphia: WB Saunders; 2011. p. 842–1002.
  10. Choong CS, Quigley CA, French FS, Wilson EM. A novel missense mutation in the amino-terminal domain of the human androgen receptor gene in a family with partial androgen insensitivity syndrome causes reduced efficiency of protein translation. J Clin Invest. 1996;98(6):1423–31. doi: 10.1172/JCI118930.
  11. Patterson MN, Hughes IA, Gottlieb B, Pinsky L. The androgen receptor gene mutations database. Nucleic Acids Res. 1994;22(17):3560–2.
  12. Chen CP, Chern SR, Wang TY, Wang W, Wang KL, Jeng CJ. Androgen receptor gene mutations in 46,XY females with germ cell tumours. Hum Reprod. 1999;14(3):664–70. doi: 10.1093/humrep/14.3.664.
  13. Hannema SE, Scott IS, Rajpert-De Meyts E, Skakkebaek NE, Coleman N, Hughes IA. Testicular development in the complete androgen insensitivity syndrome. J Pathol. 2006;208(4): 518–27. doi: 10.1002/path.1890.
  14. Coutant R, Mallet D, Lahlou N, Bouhours-Nouet N, Guichet A, Coupris L, Croué A, Morel Y. Heterozygous mutation of steroidogenic factor-1 in 46,XY subjects may mimic partial androgen insensitivity syndrome. J Clin Endocrinol Metab. 2007;92(8):2868–73. doi: 10.1210/jc.2007-0024.
  15. Davies HR, Hughes IA, Savage MO, Quigley CA, Trifiro M, Pinsky L, Brown TR, Patterson MN. Androgen insensitivity with mental retardation: a contiguous gene syndrome? J Med Genet. 1997;34(2):158–60. doi: 10.1136/jmg.34.2.158.
  16. Chang CS, Kokontis J, Liao ST. Molecular cloning of human and rat complementary DNA encoding androgen receptors. Science. 1988;240(4850):324–6. doi: 10.1126/science.3353726.
  17. Goglia U, Vinanzi C, Zuccarello D, Malpassi D, Ameri P, Casu M, Minuto F, Foresta C, Ferone D. Identification of a novel mutation in exon 1 of androgen receptor gene in an azoospermic patient with mild androgen insensitivity syndrome: case report and literature review. Fertil Steril. 2011;96(5):1165–9. doi: 10.1016/j.fertnstert.2011.08.033.
  18. Frader J, Alderson P, Asch A, Aspinall C, Davis D, Dreger A, Edwards J, Feder EK, Frank A, Hedley LA, Kittay E, Marsh J, Miller PS, Mouradian W, Nelson H, Parens E. Health care professionals and intersex conditions. Arch Pediatr Adolesc Med. 2004;158(5):426–8. doi: 10.1001/archpedi.158.5.426.
  19. Reifenstein EC Jr. Hereditary familial hypogonadism. Recent Progr Horm Res. 1947;3:224–5.
  20. Balducci R, Ghirri P, Brown TR, Bradford S, Boldrini A, Boscherini B, Sciarra F, Toscano V. A clinician looks at androgen resistance. Steroids. 1996;61(4):205–11. doi: 10.1016/0039-128x(96)00015-3.
  21. Raicu F, Giuliani R, Gatta V, Palka C, Franchi PG, Lelli-Chiesa P, Tumini S, Stuppia L. Novel mutation in the ligand-binding domain of the androgen receptor gene (l790p) associated with complete androgen insensitivity syndrome. Asian J Androl. 2008;10(4):687–91. doi: 10.1111/j.1745-7262.2008.00376.x.
  22. Mongan NP, Tadokoro-Cuccaro R, Bunch T, Hughes IA. Androgen insensitivity syndrome. Best Pract Res Clin Endocrinol Metab. 2015;29(4):569–80. doi: 10.1016/j.beem.2015.04.005.
  23. Hughes IA, Werner R, Bunch T, Hiort O. Androgen insensitivity syndrome. Semin Reprod Med. 2012;30(5):432–42. doi: 10.1055/s-0032-1324728.
  24. Batista RL, Costa EMF, Rodrigues AS, Gomes NL, Faria JA Jr, Nishi MY, Arnhold IJP, Domenice S, Mendonca BB. Androgen insensitivity syndrome: a review. Arch Endocrinol Metab. 2018;62(2):227–35. doi: 10.20945/2359-3997000000031.
  25. Massin N, Bry H, Vija L, Maione L, Constancis E, Haddad B, Morel Y, Claessens F, Young J. Healthy birth after testicular extraction of sperm and ICSI from an azoospermic man with mild androgen insensitivity syndrome caused by an androgen receptor partial loss-of-function mutation. Clin Endocrinol (Oxf). 2012;77(4):593–8. doi: 10.1111/j.1365-2265.2012.04402.x.

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Copyright (c) 2020 Dzeranova L.K., Pigarova E.A., Ivannikova E.V., Kurilo L.F., Chernykh V.B., Polyakov A.V.

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