• PMID: 10946887
• Gene Name: AR
• Condition: Idiopathic infertility, spermatogenetic defects
• Association: In this study, a proportion of males with idiopathic infertility carry relevant variations within the AR-gene. These males may be distinguished on the basis of hormone levels, calculating the ASI, although this index lacks specificity.
• Mutation: Pro390Ser, Gln798Glu
• Population size: 233
• Population details: 233 (180 males with variable impairment of spermatogenesis, 53 normal males)
• Sex: Male
• Infertility type: Male infertility
• Other associated phenotypes: Idiopathic infertility, spermatogenetic defects

Significance of mutations in the androgen receptor gene in males with idiopathic infertility

Hiort O, Holterhus PM, Horter T, Schulze W, Kremke B, Bals-Pratsch M, Sinnecker GH, Kruse K.

Abnormal human spermatogenesis is caused by a variety of genetic and acquired conditions. Because spermatogenesis is dependent on androgens, some males may have a minimal form of androgen insensitivity that does not inhibit virilization but impairs fertility. This has lead us to investigate the possibility of abnormalities in the androgen receptor (AR) gene in a large cohort of males suffering from infertility of unknown cause. We studied 180 males with variable impairment of spermatogenesis. In all patients, serum levels of testosterone and gonadotropins were analyzed to define an androgen sensitivity index (ASI). Single-strand conformation analysis and direct DNA sequencing of PCR-amplified blood leukocyte DNA were used to identify mutations within the whole coding region of the AR-gene. Endocrine and molecular investigations were compared with 53 normal males with proven fertility. In three infertile males, mutations in the AR were identified. Two unrelated males had the same variation within the first exon encoding for the transactivation domain of the receptor (Pro390Ser), whereas, in the third, a mutation in the hormone-binding region was characterized (Gln798Glu). All identified mutation carriers had a significantly elevated ASI. A proportion of males with idiopathic infertility carry relevant variations within the AR-gene. These males may be distinguished on the basis of hormone levels, calculating the ASI, although this index lacks specificity. FAU - Hiort, O AU - Hiort O AD - Department of Pediatrics, Medical University of Lübeck, Germany. FAU - Holterhus, P M AU - Holterhus PM FAU - Horter, T AU - Horter T FAU - Schulze, W AU - Schulze W FAU - Kremke, B AU - Kremke B FAU - Bals-Pratsch, M AU - Bals-Pratsch M FAU - Sinnecker, G H AU - Sinnecker GH