• PMID: 8128958
• Gene Name: AR
• Condition: X-linked Reifenstein syndrome (partial androgeninsensitivity)
• Association: Sequencing and hybridization analysis show a deletion of > 6 kb in intron 2 of the human AR gene, starting 18 bp upstream of exon 3.
• Mutation: deletion of > 6 kb in intron 2 of the human AR gene, starting 18 bp upstream of exon 3
• Population size: 1
• Population details: 1 X-linked Reifenstein syndrome (partial androgen insensitivity)
• Sex: Male
• Infertility type: Male infertility, Female infertility
• Other associated phenotypes: X-linked Reifenstein syndrome (partial androgen insensitivity)

Differential splicing of human androgen receptor pre-mRNA in X-linked Reifenstein syndrome, because of a deletion involving a putative branch site

Ris-Stalpers C, Verleun-Mooijman MC, de Blaeij TJ, Degenhart HJ, Trapman J, Brinkmann AO.

The analysis of the androgen receptor (AR) gene, mRNA, and protein in a subject with X-linked Reifenstein syndrome (partial androgen insensitivity) is reported. The presence of two mature AR transcripts in genital skin fibroblasts of the patient is established, and, by reverse transcriptase-PCR and RNase transcription analysis, the wild-type transcript and a transcript in which exon 3 sequences are absent without disruption of the translational reading frame are identified. Sequencing and hybridization analysis show a deletion of > 6 kb in intron 2 of the human AR gene, starting 18 bp upstream of exon 3. The deletion includes the putative branch-point sequence (BPS) but not the acceptor splice site on the intron 2/exon 3 boundary. The deletion of the putative intron 2 BPS results in 90% inhibition of wild-type splicing. The mutant transcript encodes an AR protein lacking the second zinc finger of the DNA-binding domain. Western/immunoblotting analysis is used to show that the mutant AR protein is expressed in genital skin fibroblasts of the patient. The residual 10% wild-type transcript can be the result of the use of a cryptic BPS located 63 bp upstream of the intron 2/exon 3 boundary of the mutant AR gene. The mutated AR protein has no transcription-activating potential and does not influence the transactivating properties of the wild-type AR, as tested in cotransfection studies. It is concluded that the partial androgen-insensitivity syndrome of this patient is the consequence of the limited amount of wild-type AR protein expressed in androgen target cells, resulting from the deletion of the intron 2 putative BPS. FAU - Ris-Stalpers, C AU - Ris-Stalpers C AD - Department of Endocrinology and Reproduction, Erasmus University, Rotterdam, The Netherlands. FAU - Verleun-Mooijman, M C AU - Verleun-Mooijman MC FAU - de Blaeij, T J AU - de Blaeij TJ FAU - Degenhart, H J AU - Degenhart HJ FAU - Trapman, J AU - Trapman J