Identification Of Novel Single Nucleotide Polymorphisms In Androgen Receptor Gene In Two Families With Complete Androgen Insensitivity Syndrome

The present study aimed to identify novel mutations in androgen receptor (AR) gene associated with complete androgen insensitivity syndrome (AIS). Genome DNA was extracted from peripheral blood of 35 suspected patients and their genetic relatives. All participants' karyotypes were analyzed. Single nucleotide polymorphisms (SNPs) in the AR gene (Genebank accession no.: NM_000044.2) were analyzed by sequencing. Among the patients, 3 SNPs in the AR gene were identified. Two out of the 3 SNPs were detected in 2 families with complete AIS. The proband of one family was a 3-year-old girl (a 46, XY karyotype) and normal intelligence. She was hospitalized for irreversible lump in the right inguinal canal. One SNP in the AR gene (c.2521C>A, p.R840S) was identified in the proband. The proband's mother (healthy) and her aunt IV2 (showing complete AIS) carried the same SNP in the AR gene. However, her father did not carry this variant. Another AR SNP (c.946T>V, p.Y316H) was detected in a 20-month-old boy (46, XY) and 3 other members of a second family. His mother and grandmother carried this SNP but did not present AIS. His uncle was a homozygous carrier and declared no signs of AIS. The 2 affected probands underwent surgery and pathological tests confirmed the excised tissue as the testis tissue. In conclusion, we report 2 novel mutations in AR gene (i.e., c.2521C>A and c.946T>V), which are associated with the development of complete AIS.