Functional assessment and clinical classification of androgen sensitivity in patients with mutations of the androgen receptor gene

@article{Sinnecker1996FunctionalAA,
  title={Functional assessment and clinical classification of androgen sensitivity in patients with mutations of the androgen receptor gene},
  author={Gernot H. G. Sinnecker and Olaf Hiort and Esther M. Nitsche and P. M. Holterhus and Klaus Kruse and German Neuromonitoring Study Group},
  journal={European Journal of Pediatrics},
  year={1996},
  volume={156},
  pages={7-14}
}
Abstract In the genetic male, mutations of the androgen receptor (AR) gene cause phenotypes ranging from female to subfertile male. Binding assays on genital skin fibroblasts and DNA analysis alone provide incomplete information about receptor function. We used the sex hormone-binding globulin (SHBG) response to stanozolol as a measure of AR function and correlated the results with phenotypes which were classified according to the degree of defective masculinization. Of the 34 patients… 

Phenotypic Heterogeneity Associated with Identical Mutations in Residue 870 of the Androgen Receptor

P phenotypic heterogeneity associated to identical mutations in the AR gene is probably due to individual functional differences in AR coregulator molecules, and this results in an AIS characterized by bilateral gynecomastia, normal male external genitalia, and normal sperm counts.

In-vitro Characterization of Androgen Receptor Mutations Associated with Complete Androgen Insensitivity Syndrome Reveals Distinct Functional Deficits

It is concluded that mutations in the AR have to be characterized meticulously, not only to prove any quantitative functional deficit as a proof of consequence, but also to gain knowledge on qualitative functional properties.

Investigation of androgen receptor gene mutations in a series of 21 patients with 46,XY disorders of sex development

This study investigates AR gene mutations in 46,XY DSD patients with normal testosterone secretion, either normal or high testosterone/dihydrotestosterone (T/DHT) ratio and normal SRD5A2 gene analysis, collectively, suggestive of androgen insensitivity syndrome (AIS).

A Novel Point Mutation in the Hormone Binding Domain of the Androgen Receptor Associated with Partial and Minimal Androgen Insensitivity Syndrome

It is concluded that phenotypic variations in mild AR defects are striking and can remain undetected even until late in life.

Molecular features and clinical phenotypes in androgen insensitivity syndrome in the absence and presence of androgen receptor gene mutations

Patients with clinically evident complete androgen insensitivity syndrome are likely to harbor an AR gene mutation, demanding that the two polymorphic regions must always be included in molecular analyses of the AR gene.

Mosaicism due to a somatic mutation of the androgen receptor gene determines phenotype in androgen insensitivity syndrome.

Somatic mosaicism of the AR gene can represent a substantial factor for the individual phenotype by shifting it to a higher degree of virilization than expected from the genotype of the mutant allele alone.

Novel molecular defects in the androgen receptor gene of Mexican patients with androgen insensitivity

The view that nonsense mutations in the AR results almost invariably in a CAIS phenotype and underly the importance of the steroid‐binding domain (SBD) for the AR functional activity is reaffirmed.

Expression of two functionally different androgen receptors in a patient with androgen insensitivity

The present case clearly demonstrates the molecular mechanism by which somatic mosaicism of the androgen receptor gene can modulate in vivo androgen action and underlines the importance of particular notice on somatic mosaicicism in all androgen insensitivity syndrome patients carrying de novo mutations of the AR gene.

The Molecular Basis of Androgen Insensitivity

Androgen insensitivity syndrome (AIS) as the clinical entity of defective androgen action with variable phenotypes in 46,XY patients is caused by mutations of the X-chromosomal AR gene.

Phenotypic variation in a family with partial androgen insensitivity syndrome explained by differences in 5alpha dihydrotestosterone availability.

The distinct phenotypic variation in AIS here is explained by differences in the availability of 5alpha-dihydrotestosterone during embryonic sex differentiation.
...

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  • I. HughesB. Evans
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    The Journal of clinical endocrinology and metabolism
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A new variant of CAIS is described which is characterized by an increased concentration of androgen receptors that appear to be quantitatively and qualitatively normal.

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