1/131. Complete androgen insensitivity caused by a splice donor site mutation in intron 2 of the human androgen receptor gene resulting in an exon 2-lacking transcript with premature stop-codon and reduced expression.Various mutations within the human androgen receptor gene have been documented to cause defective sexual differentiation in karyotypic male individuals. In this study, we report a previously undescribed point mutation at the donor splice-site of the second intron of the androgen receptor gene in a patient with a completely female phenotype. The sequence alteration was detected by single-strand-conformation-analysis-PCR and genomic sequencing. Applying competitive reverse transcribed PCR, cDNA sequencing and Western blotting, we could demonstrate considerable aberrations of structure and concentration of the transcript and its translation product in the patient's fibroblasts from the genital region. (1) In the transcript, exon 1 and 3 are directly linked to each other, the complete second exon is skipped. The mRNA predictively suffers a codon frame-shift in exon 3 associated with a premature termination between codons 598 and 599, leading to a truncated androgen receptor protein lacking any in vivo function. (2) Steady-state concentration levels of transcript and protein are abnormally low. Our observations highlight the influence of exon-flanking intron sequences on proper expression and function of gene products.- - - - - - - - - - ranking = 1keywords = androgen (Clic here for more details about this article) |
2/131. An androgen receptor mutation in the direct vicinity of the proposed C-terminal alpha-helix of the ligand binding domain containing the AF-2 transcriptional activating function core is associated with complete androgen insensitivity.Subjects with androgen insensitivity syndromes (AIS) are characterized by a 46, XY karyotype, presence of testes, normal or elevated androgen levels in blood, and impairment of the usual response to androgens associated with various aberrations of male differentiation and virilization ranging from slightly undervirilized men to phenotypic females. Here we describe a novel proline to serine mutation in codon 892 (exon 8) of the androgen receptor in a patient with complete androgen insensitivity. The mutation is located in the direct vicinity of the proposed C-terminal alpha-helix of the ligand binding domain containing the AF-2 transcriptional activating function core. Investigation of androgen binding in cultured testicular fibroblasts of the patient revealed a reduced AR binding capacity (11 fmol/mg protein) and a highly elevated Kd value (3.1 nM) in comparison to control genital skin fibroblasts. Cotransfection studies with an androgen-responsive reporter gene revealed a diminished transactivation property of the mutant androgen receptor.- - - - - - - - - - ranking = 1.4545454545455keywords = androgen (Clic here for more details about this article) |
3/131. Complete androgen insensitivity caused by a new frameshift deletion of two base pairs in exon 1 of the human androgen receptor gene.We describe a novel mutation in exon 1 of the androgen receptor gene in a patient with complete androgen insensitivity (CAIS). Endocrine findings were typical for androgen insensitivity (testosterone serum levels in the upper limit of normal males and increased LH serum concentrations). Biochemical investigations in cultured genital skin fibroblasts of the patient showed a normal 5alpha-reductase activity but a complete absence of androgen binding. Western blot analysis revealed no detectable protein product. sequence analysis of the entire coding region of the androgen receptor gene resulted in the identification of a 2-bp deletion in codon 472, causing frameshift and introduction of a premature stop codon 27 codons downstream of the mutation.- - - - - - - - - - ranking = 1.1818181818182keywords = androgen (Clic here for more details about this article) |
4/131. A case of complete testicular feminization: laparoscopic orchiectomy and analysis of androgen receptor gene mutation.BACKGROUND: Analysis of an androgen receptor gene mutation and a bilateral laparoscopic orchiectomy were performed on a 19-year-old patient diagnosed as a case of complete testicular feminization. methods: dna sequencing of an androgen receptor gene mutation and laparoscopic orchiectomy were performed. RESULTS: A novel point mutation substituting a proline residue (CCG) for a leucine residue (CTG) was observed in codon 892 of exon 8 in the hormone-binding domain of the androgen receptor gene. Bilateral intra-abdominal testes were resected uneventfully by means of laparoscopic orchiectomy. CONCLUSION: We conclude that genetic analysis of androgen receptor gene mutation is essential for diagnosis of teon and laparoscopic orchiectomy is a useful therapeutic alteration as a minimally invasive treatment.- - - - - - - - - - ranking = 0.72727272727273keywords = androgen (Clic here for more details about this article) |
5/131. A frame shift mutation in the dna-binding domain of the androgen receptor gene associated with complete androgen insensitivity, persistent mullerian structures, and germ cell tumors in dysgenetic gonads.OBJECTIVE: To describe the molecular, cytogenetic, immunohistochemical, and endocrinologic characteristics of a young 46,XY female with persistent mullerian structures and germ cell tumors in dysgenetic gonads. DESIGN: Descriptive case study. SETTING: Mackay Memorial Hospital and National Yang-Ming University, Taipei, taiwan. PATIENT(S): A 22-year-old 46,XY female with persistent mullerian structures, a low level of serum testosterone, and no apparent adnexal masses. INTERVENTION(S): Laparoscopic removal of the dysgenetic gonads. MAIN OUTCOME MEASURE(S): Detection of an androgen receptor gene mutation by a semiautomated dna sequencer, of the chromosomal complement by cytogenetic examination, of placental alkaline phosphatase activity by immunohistochemical analysis, and of neoplasms in dysgenetic gonads by histologic studies. RESULT(S): A unilateral gonadoblastoma and a contralateral gonadoblastoma associated with a dysgerminoma were found in the excised gonads. The tumors had a 46,XY complement. Placental alkaline phosphatase was present in the tumor cells. A frameshift mutation in the dna-binding domain of the androgen receptor gene was detected in the patient's blood and the tumor tissues. A five-nucleotide "AGGAA" deletion at codons 608 and 609 of the androgen receptor gene resulted in a missing arginine and lysine as well as a frameshift that introduced a stop codon 12 amino acid downstream from the mutation. CONCLUSION(S): Molecular genetic analysis of the androgen receptor gene aids in the rapid diagnosis of complete androgen insensitivity irrespective of atypical clinical phenotypes and endocrinologic parameters.- - - - - - - - - - ranking = 1.1818181818182keywords = androgen (Clic here for more details about this article) |
6/131. Complete androgen insensitivity in a 47,XXY patient with uniparental disomy for the x chromosome.We describe a unique patient with complete androgen insensitivity syndrome and a 47,XXY karyotype. Androgen receptor assay using cultured pubic skin fibroblasts showed no androgen-binding capacity. sequence analysis of the androgen receptor gene demonstrated two nonsense mutations, one in exon D and one in exon E. Microsatellite marker analysis showed that the patient is homozygous for all five Xq loci examined. The results suggest that the long-arms of the two X chromosomes are identical, i.e., uniparental isodisomy at least for Xq, and carry the same mutations in the androgen receptor gene. This explains how complete androgen insensitivity syndrome occurred in this 47,XXY individual.- - - - - - - - - - ranking = 0.81818181818182keywords = androgen (Clic here for more details about this article) |
7/131. A new point mutation of the androgen receptor gene in a patient with partial androgen resistance and severe oligozoospermia.Mutations of the androgen receptor gene in genetic males cause a variety of androgen insensitivity syndromes varying from female phenotype through intersexuality to male phenotype with infertility. The identification of a missense mutation in the steroid-binding domain in an infertile male with mild features of androgen insensitivity is reported here.- - - - - - - - - - ranking = 1keywords = androgen (Clic here for more details about this article) |
8/131. Expression of two functionally different androgen receptors in a patient with androgen insensitivity.Recently, we demonstrated a previously unknown high rate of de novo mutations of the androgen receptor (AR) gene in androgen insensitivity syndrome (AIS) with some resulting in somatic mosaicism of mutant and wild type AR alleles. However, data on the genotype-phenotype relationship in the latter patients are sparse. We present here a 46,XY newborn with ambiguous genitalia carrying a mosaic of an 866 GTG (Val) --> ATG (Met) mutation with the wild type AR gene. This mutation has usually been associated with complete AIS. Accordingly, we found markedly impaired transactivation due to the mutant Met866 AR. Essential information arose from Scatchard analysis of methyltrienolone binding on cultured genital skin fibroblasts. We demonstrated for the first time the expression of two functionally different ARs (Kd1: 5.58 nM = mutant, Kd2: 0.06 nM = wild type) in one AIS individual. This finding not only represents an important confirmation for the presence of the somatic mosaicism in the patient, it also indicates the most likely molecular mechanism responsible for the unexpectedly strong virilization of the patient: Androgen action through the wild type AR expressed by part of the somatic cells. The present case clearly demonstrates the molecular mechanism by which somatic mosaicism of the androgen receptor gene can modulate in vivo androgen action. It underlines the importance of particular notice on somatic mosaicism in all androgen insensitivity syndrome patients carrying de novo mutations of the androgen receptor gene.- - - - - - - - - - ranking = 1.2727272727273keywords = androgen (Clic here for more details about this article) |
9/131. Directed pharmacological therapy of ambiguous genitalia due to an androgen receptor gene mutation.We report a 46,XY infant with an M807T mutation in his androgen receptor that abrogated cellular responses to testosterone, but not to dihydrotestosterone (DHT), resulting in ambiguous genitalia. Treatment with a topical DHT gel restored male genital development allowing the infant to be reared in accordance with his chromosomal sex.- - - - - - - - - - ranking = 0.45454545454545keywords = androgen (Clic here for more details about this article) |
10/131. Analysis of exon 1 mutations in the androgen receptor gene.Eleven mutations in exon 1 of the androgen receptor gene (AR) have been identified in 15 individuals with Androgen Insensitivity syndrome (AIS). Nine of the mutations yield a stop codon directly, or due to a frameshift, in individuals with complete AIS (CAIS). One individual with CAIS had three different mutations in exon 1: one is nominally silent (Glu 211; GAG 995 GAA); two are missense (Pro 390 Arg and Glu 443 Arg). Five unrelated individuals with either CAIS, partial AIS (PAIS) or mild AIS (MAIS) had GAG 995 GAA as their only alteration. This report almost doubles the number of exon 1 mutations stored in the AR Mutation database, reinforces their highly predominant nonsense character, and identifies Pro 390 and/or Gln 443 as residues that are probably necessary for one or more specific functions of the AR's N-terminal transactivation domain.- - - - - - - - - - ranking = 0.45454545454545keywords = androgen (Clic here for more details about this article) |
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