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Background
The human androgen receptor (AR) is an essential steroid hormone receptor that plays a critical role in male sexual differentiation, development and preservation of the male phenotype, ignition and maintenance of spermatogenesis. 1 It is characterised by a modular structure consisting of four functional domains: an N-terminal domain, which serves transcriptional activation function; a central DNA-binding domain rich in cysteine residues; a hinge region containing the nuclear targeting signal and a C-terminal ligand-binding domain (LBD). LBD plays a critical role in nuclear localisation, receptor dimerisation and interaction with other proteins in addition to ligand binding. 2 3 In humans, AR is a 110 kDa protein composed of 919 amino acids that are encoded by the AR gene located on the X chromosome at Xq11-12 and has eight exons. 4
Mutations in the AR gene cause malfunctioning of the AR function, including loss of function, AR alterations and gain of function, many of which are associated with androgen insensitivity syndrome (AIS) (OMIM no 300068). 5
AIS is a recessive genetic disorder composed of three different classes based on phenotype: complete androgen insensitivity syndrome (CAIS), partial androgen insensitivity syndrome (PAIS) and mild androgen insensitivity syndrome (MAIS). 6 Individuals with CAIS syndrome have female external genitalia with normal labia, clitoris and vaginal introitus, whereas those with PAIS syndrome have various degrees of ambiguous genitalia, including partial labial scrotal fusion, hypospadias, bifid scrotum and gynecomastia. By contrast, MAIS individuals have a moderate presentation with major complaint of disruption in the spermatogenesis process without any abnormalities in their secondary male sexual characteristics. 7 Since 2004, the number of reported mutations in the AR gene increased from 605 to 1029; these mutations have been linked to prostate cancer, male infertility and breast cancer. 8 Recent studies have suggested a connection between specific AR mutations and idiopathic male infertility. 9 Identification of such mutations is essential for precise diagnosis and managements. In this study, we present a point mutation in the AR gene found in two unrelated infertile men.
Case presentation
Two unrelated men aged 40 and 36 years were referred to Orient Hospital in Damascus Syria for reproductive counselling and treatment. Their main complaint was primary male infertility for 10 and 8 years, respectively. Their wives aged 34 and 32...