Background:
Androgen receptor (AR) is an X-linked gene essential for spermatogenesis. Many Some AR gene mutations leading to amino acid substitution may alter the structure or function of the protein and subsequently impact fertility. Several mutations in the AR gene have been found that can make complete androgen insensitivity syndrome (CAIS), partial androgen insensitivity syndrome (PAIS) or mild androgen insensitivity syndrome (MAIS) in infertile men.Case presentation: Here, we report a missense mutation in a 30-year-old man with idiopathic azoospermia, caused by sperm maturation arrest (MA) at spermatid stage. His family history was unremarkable and his brother had fathered normal children. Hormonal analysis of serum LH, FSH and testosterone was performed in this case. The AR cDNA was prepared from tissue mRNA and were amplified by PCR. The sequencing results revealed a missense point mutation that caused by cDNA nucleotide change 3323 G > A. It was a known pathogenic mutation, which had been reported previously in a patients with CAIS [MIM:300068]. Only Aspartic Acid was found at this position. Several prediction tools were used to predict the pathogenicity demonstrated that p. D733N nonsynonymous variant would affect protein structure and its normal function.Discussion & Conclusion: Literature data suggest that the typical phenotype in individuals with p.D733N mutation include female genital phenotype and male karyotype, Our case report shows that p.D733N mutation could be associated also with a milder phenotype, characterized by an infertile man. There is a difference in charge between the wild-type and mutant amino acid. The wild-type residue forms a salt bridge with Lysine at position 823. It is very interesting that mutations in the AR gene causing p.D733N substitution, resulted in different clinical manifestations. It is possible that mutation in other parts of the AR or other genes are is modified phenotype. However, the effect of the Gln rich N-terminal region of the AR and post-translational modifications should also be considered. Disruption of the tertiary structure of the AR protein would likely cause a series of changes in domain functionality which is moderated by an unknown factor. Hence we can t just rely on AR mutations to predict the outcome, as illustrated in this case.