• PMID: 10502786
• Gene Name: AR
• Condition: PAIS
• Association: A novel point mutation (R840S) in the androgen receptor in a Brazilian family with partial androgeninsensitivity syndrome.
• Mutation: Patient mutation:R840S, Other known mutations: R840C, R840G, R840H
• Population size: 2
• Population details: 2 PAIS
• Sex: Male
• Infertility type: Male infertility
• Other associated phenotypes: Male infertility

A novel point mutation (R840S) in the androgen receptor in a Brazilian family with partial androgen insensitivity syndrome

Melo KF, Latronico AC, Costa EM, Billerbeck AE, Mendonca BB, Arnhold IJ.

Mutations of the androgen receptor gene causing androgen insensitivity syndrome in 46, XY individuals, result in phenotypes ranging from complete female to ambiguous genitalia to males with minor degrees of undervirilization. We studied two Brazilian brothers with partial androgen insensitivity syndrome. They were born with perineal hypospadias, bifid scrotum, small penis and cryptorchidism, and developed gynecomastia at puberty. Genomic DNA was extracted and denaturinggradient gel electrophoresis of exon 7 of the androgen receptor gene followed by sequence analysis revealed a new mutation, a C A transversion, altering codon 840 from arginine (CGT) to serine (AGT). R840 is located in the androgen binding domain, in a "hot spot" region, important for the formation and function of the hormone receptor-complex and within the region that is involved in androgen receptor dimerization. Replacement of arginine (basic) by serine (neutral and polar) is a nonconservative substitution. Three mutations in this residue (R840C, R840G nonconservative and R840H, conservative) were previously reported in patients with partial androgen insensitivity syndrome and when expressed "in vitro" lead to a subnormal transactivation of a reporter gene. We conclude that the novel R840 mutation in the androgen receptor is the cause of partial androgen insensitivity syndrome in this Brazilian family. CI - Copyright 1999 Wiley-Liss, Inc. FAU - Melo, K F AU - Melo KF AD - Hospital das Clínicas, Laboratório de Hormônios e Genética Molecular (LIM 42), Universidade de São Paulo, São Paulo, Brasil. FAU - Latronico, A C AU - Latronico AC FAU - Costa, E M AU - Costa EM FAU - Billerbeck, A E AU - Billerbeck AE FAU - Mendonca, B B AU - Mendonca BB