Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0042755 (masculinization)
 2,562 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Androgen resistance in genetic males occurs when gonadotropins and testosterone are normal, but the physiological androgen response in androgen target organs is absent or decreased. In androgen-dependent target tissues two main defects may be found: 1) defective testosterone metabolism (5 alpha-reductase type 2 deficiency) and 2) anomalies in androgen receptors (androgen insensitivity syndrome (AIS)). The clinical manifestations of these defects vary from subjects with female external genitalia to subjects with mild forms of impaired masculinization. In particular, in the complete form of AIS (CAIS) the phenotype is feminine, and in the partial form (PAIS) the external genitalia are ambiguous with an extremely variable phenotype. The diagnosis requires clinical, hormonal, genetic, and molecular investigation for appropriate gender assignation and treatment. In AIS, cloning of androgen receptor cDNA using the polymerase chain reaction, denaturing gradient gel electrophoresis, and nucleotide sequencing have enabled a variety of molecular defects in the androgen receptor to be identified. The complexity of phenotypic presentation of AIS probably reflects the heterogeneity of androgen receptor gene mutations, but to date a relationship between genotype/phenotype has been difficult to establish, with the same point mutation reported to be associated with different phenotypic expressions. Other factors must therefore also contribute to the clinical presentation of AIS, although none have yet been identified. Establishing the functional consequences of androgen receptor mutations in vitro systems and correlating them with clinical presentation may ultimately provide an explanation for the variable clinical presentation of AIS and perhaps enable prediction of the response to androgen therapy in infants with PAIS.
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PMID:A clinician looks at androgen resistance. 873 2

Androgen insensitivity syndrome (AIS) is a rare X-linked recessive condition in which patients with 46,XY karyotype have a complete (CAIS) or partial (PAIS) impairment of pre- and postnatal virilization due to mutations in the androgen receptor (AR). We present a concise revision of AIS and the AR and report the clinical, hormonal and molecular study of 33 subjects with AIS. The coding region of the AR was analyzed in 33 subjects with clinical and hormonal characteristics that suggested AIS. Eleven patients (9 families) had CAIS and 22 patients (12 families) had PAIS. Mutations in the AR were identified and the molecular diagnosis of AIS established in 100% of families with CAIS and 75% with PAIS. Nine mutations had been previously described (N705S, W741C, M742V, R752X, Y763C, R779W, M807V, R855C e R855H) and 7 mutations were first described in these cohort of patients (S119X, T602P, L768V, R840S, I898F, P904R e IVS3 - 60 G>A).
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PMID:[Androgen insensitivity syndrome: clinical, hormonal and molecular analysis of 33 cases]. 1654 39

Androgenic insensitivity syndrome is the most common cause of disorders of sexual differentiation in 46,XY individuals. It results from alterations in the androgen receptor gene, leading to a frame of hormonal resistance, which may present clinically under 3 phenotypes: complete (CAIS), partial (PAIS) or mild (MAIS). The androgen receptor gene has 8 exons and 3 domains, and allelic variants in this gene occur in all domains and exons, regardless of phenotype, providing a poor genotype - phenotype correlation in this syndrome. Typically, laboratory diagnosis is made through elevated levels of LH and testosterone, with little or no virilization. Treatment depends on the phenotype and social sex of the individual. Open issues in the management of androgen insensitivity syndromes includes decisions on sex assignment, timing of gonadectomy, fertility, physcological outcomes and genetic counseling.
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PMID:Androgen insensitivity syndrome: a review. 2976 28