Altered mRNA Expression due to Insertion or Substitution of Thymine at Position +3 of Two Splice-Donor Sites in the Androgen Receptor Gene

Trifiro, Mark; Lumbroso, Rose; Beitel, Lenore K.; Vasiliou, D. Marie; Bouchard, Joanne; Deal, Cheri; Vliet, Guy Van; Pinsky, Leonard

doi:10.1159/000484731

Cited by 10 publications

(4 citation statements)

References 21 publications

(35 reference statements)

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“…Trifiro et al (39) described a mutation very similar to that reported here, an A T mutation in ϩ3 donor splice site of intron 6, that resulted in a CAIS phenotype. However, even though they could detect a small amount of normal mRNA, unlike in our report they were not able to detect AR protein expression.…”

Section: Discussionsupporting

confidence: 72%

“…Among these, five are transversions G3 T, as in our study, and they result in the skipping of relative exons (33)(34)(35)(36) or activation of a cryptic site (37). Some of these cases concern insertions, intronic deletions, or mutations outside the splicing region (21,22,39,40). Some of these cases concern insertions, intronic deletions, or mutations outside the splicing region (21,22,39,40).…”

Section: Discussionmentioning

confidence: 99%

“…Alterations affecting AR gene splicing are very rare (ϳ3%) (38), and in a few cases abnormal splicing has been associated with AIS. In other cases, point mutations in the consensus sequence donor splice site have been described, causing excision of the exons 2, 3, 6, and 7 (39,(41)(42)(43) or activation of a cryptic splice donor site in exon 4 (44). In other cases, point mutations in the consensus sequence donor splice site have been described, causing excision of the exons 2, 3, 6, and 7 (39,(41)(42)(43) or activation of a cryptic splice donor site in exon 4 (44).…”

Section: Discussionmentioning

confidence: 99%

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Novel Point Mutation in the Splice Donor Site of Exon-Intron Junction 6 of the Androgen Receptor Gene in a Patient with Partial Androgen Insensitivity Syndrome*

Sammarco

Grimaldi

Rossi

et al. 2000

The Journal of Clinical Endocrinology &Amp; Metabolism

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Androgen receptor (AR) gene mutations have been shown to cause androgen insensitivity syndrome with altered sexual differentiation in XY individuals, ranging from a partial insensitivity with male phenotype and azoospermia to a complete insensitivity with female phenotype and the absence of pubic and axillary sexual hair after puberty. In this study we present an 11-yr-old XY girl, with clinical manifestations peculiar for impaired androgen biological action, including female phenotype, blind-ending vagina, small degree of posterior labial fusion, and absence of uterus, fallopian tubes, and ovaries. At the time of the diagnosis the patient had a FSH/LH ratio according to the puberal stage, undetectable 17beta-estradiol, and high levels of testosterone (80.1 ng/mL). After bilateral gonadectomy, performed at the age of 11 yr, histological examination showed small embryonic seminiferous tubules containing prevalently Sertoli cells and occasional spermatogonia together with abundant fibrous tissue. Molecular study of the patient showed a guanine to thymine transversion in position +5 of the donor splice site in the junction between exon 6 and intron 6 of the AR gene. The result of RT-PCR amplification of the AR messenger ribonucleic acid from cultured genital skin fibroblasts of the patient suggests that splicing is defective, and intron 6 is retained in most of the receptor messenger ribonucleic acid molecules. We show by immunoblotting that most of the expressed protein lacks part of the C-terminal hormone-binding domain, and a small amount of normal receptor is observed. This is probably responsible for the reduced binding capacity in genital skin fibroblasts of the patient. The molecular basis of the alteration in this case is a novel, uncommon mutation, leading to a phenotype indicative of a partial androgen insensitivity syndrome, Quigley's grade 5.

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Section: Discussionsupporting

confidence: 72%

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

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Novel Point Mutation in the Splice Donor Site of Exon-Intron Junction 6 of the Androgen Receptor Gene in a Patient with Partial Androgen Insensitivity Syndrome*

Sammarco

Grimaldi

Rossi

et al. 2000

The Journal of Clinical Endocrinology &Amp; Metabolism

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“…In one study, seven out of eight reported cases of substitution mutations in donor splice sites, were patients with CAIS (Greep, ). Insertion of a nucleotide at a splice donor site in intron 6 caused PAIS in one case (Trifiro et al ., ). As for splice acceptor sites, only three mutations have been reported which all alter the effective splicing of the AR mRNA.…”

Section: Introductionmentioning

confidence: 97%

Androgen receptor‐related diseases: what do we know?

et al. 2016

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SUMMARYThe androgen receptor (AR) and the androgen-AR signaling pathway play a significant role in male sexual differentiation and the development and function of male reproductive and non-reproductive organs. Because of AR's widely varied and important roles, its abnormalities have been identified in various diseases such as androgen insensitivity syndrome, spinal bulbar muscular atrophy, benign prostatic hyperplasia, and prostate cancer. This review provides an overview of the function of androgens and androgen-AR mediated diseases. In addition, the diseases delineated above are discussed with respect to their association with mutations and other post-transcriptional modifications in the AR. Finally, we present an introduction to the potential therapeutic application of most recent pharmaceuticals including miRNAs in prostate cancer that specifically target the transactivation function of the AR at post-transcriptional stages.

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