Aberrant splicing of androgenic receptor mRNA results in synthesis of a nonfunctional receptor protein in a patient with androgen insensitivity

Journal Article · Mon Oct 01 00:00:00 EDT 1990 · Proceedings of the National Academy of Sciences of the United States of America; (USA)

DOI:https://doi.org/10.1073/pnas.87.20.7866· OSTI ID:5545406

Ris-Stalpers, C; Kuiper, G G.J.M.; Faber, P W; van Rooij, H C.J.; Degenhart, H J; Trapman, J; Brinkmann, A O ^[1]; Schweikert, H U ^[2]; Zegers, N D ^[3]; Hodgins, M B ^[4]

---

1. Erasmus Univ., Rotterdam (Netherlands)
2. Univ. of Bonn (Germany)
3. Medical Biological Laboratory-Organization for Applied Scientific Research, Rijswijk (Netherlands)
4. Glasgow Univ. (United Kingdom)

Androgen insensitivity is a disorder in which the correct androgen response in an androgen target cell is impaired. The clinical symtpoms of this X chromosome-linked syndrome are presumed to be caused by mutations in the androgen receptor gene. The authors report a G {r arrow} T mutation in the splice donor site of intron 4 of the androgen receptor gene of a 46, XY subject lacking detectable androgen binding to the receptor and with the complete form of androgen insensitivity. This point mutation completely abolishes normal RNA splicing at the exon 4/intron 4 boundary and results in the activation of a cryptic splice donor site in exon 4, which leads to the deletion of 123 nucleotides from the mRNA. Translation of the mutant mRNA results in an androgen receptor protein {approx}5 kDa smaller than the wild type. This mutated androgen receptor protein was unable to bind androgens and unable to activate transcription of an androgen-regulated reporter gene construct. This mutation in the human androgen receptor gene demonstrates the importance of an intact steroid-binding domain for proper androgen receptor functioning in vivo.

• OSTI ID: 5545406
• Journal Information: Proceedings of the National Academy of Sciences of the United States of America; (USA), Vol. 87:20; ISSN 0027-8424
• Country of Publication: United States
• Language: English

Related Subjects

59 BASIC BIOLOGICAL SCIENCES
ESTROGENS
RADIORECEPTOR ASSAY
MEMBRANE PROTEINS
BIOSYNTHESIS
MESSENGER-RNA
TRANSCRIPTION
ANDROGENS
DNA BASE TRANSITIONS
GENE AMPLIFICATION
GENE MUTATIONS
HEREDITARY DISEASES
PATIENTS
RECEPTORS
TRITIUM COMPOUNDS
ANDROSTANES
DISEASES
HORMONES
HYDROGEN COMPOUNDS
ISOTOPE APPLICATIONS
MUTATIONS
NUCLEIC ACIDS
ORGANIC COMPOUNDS
PROTEINS
RNA
STEROID HORMONES
STEROIDS
SYNTHESIS
TRACER TECHNIQUES
550201* - Biochemistry- Tracer Techniques