Exactly what causes this variation is not entirely understood, although factors contributing to it could include the lengths of the polyglutamine and polyglycine tracts, sensitivity to and variations in the intrauterine endocrine milieu, the effect of coregulatory proteins active in Sertoli cells, somatic mosaicism, expression of the 5RD2 gene in genital skin fibroblasts, reduced AR transcription and translation from factors other than mutations in the AR coding region, an unidentified coactivator protein, enzyme deficiencies such as 21-hydroxylase deficiency, or other genetic variations such as a mutant steroidogenic factor-1 protein. The degree of variation, however, does not appear to be constant across all AR mutations, and is much more extreme in some. Missense mutations that result in a single amino acid substitution are known to produce the most phenotypic diversity. Pathophysiology
Androgens and the androgen receptor
The effects that androgens have on the human body (virilization, masculinization, anabolism, etc.) are not brought about by androgens themselves, but rather are the result of androgens bound to androgen receptors; the androgen receptor mediates the effects of androgens in the human body.
Congenital stromal corneal dystrophy (CSCD) is an extremely rare, autosomal dominant form of corneal dystrophy. Only 4 families have been reported to have the disease by 2009. The main features of the disease are numerous opaque flaky or feathery areas of clouding in the stroma that multiply with age and eventually preclude visibility of the endothelium. Strabismus or primary open angle glaucoma was noted in some of the patients. Thickness of the cornea stays the same, Descemets membrane and endothelium are relatively unaffected, but the fibrils of collagen that constitute stromal lamellae are reduced in diameter and lamellae themselves are packed significantly more tightly. Genetics
CSCD is associated with a mutation in the gene DCN that encodes the protein decorin, located at chromosome 12q22. The disorder is inherited in an autosomal dominant manner, which indicates that the defective gene responsible for a disorder is located on an autosome (chromosome 12 is an autosome), and only one copy of the gene is sufficient to cause the disorder, when inherited from a parent who has the disorder. Diagnosis
Treatment
References
External links
GeneReviews/NCBI/NIH/UW entry on Congenital Stromal Corneal Dystrophy