A recurrent synonymous mutation in the human androgen receptor gene causing complete androgen insensitivity syndrome

Autor(es)

Batista, Rafael Loch ^[1] ; Rodrigues, Andresa di Santi ^[1] ; Nishi, Mirian Yumie ^[1] ; Gomes, Nathalia Lisboa ^[1] ; Diniz Faria Junior, Jose Antonio ^[1] ; de Moraes, Daniela Rodrigues ^[1] ; Carvalho, Luciani Renata ^[1] ; Frade Costa, Elaine Maria ^[1] ; Domenice, Sorahia ^[1] ; Mendonca, Berenice Bilharinho ^[1]

Afiliação do(s) autor(es)

^[1] Univ Sao Paulo, Lab Hormonios & Genet Mol LIM42, Unidade Endocrinol Desenvolvimento, Discipline Endocrinol & Metab, Hosp Clin, Fac Med, Sao Paulo - Brazil

• Tipo de documento: Artigo Científico
• Fonte: JOURNAL OF STEROID BIOCHEMISTRY AND MOLECULAR BIOLOGY; v. 174, p. 14-16, NOV 2017.
• Citações Web of Science: 8

Resumo

Androgen insensitivity syndrome (AIS) is the most common cause of 46,XY disorders of sex development (46,XY DSD). This syndrome is an X-linked inheritance disease and it is caused by mutations in the human androgen receptor (AR) gene. Non-synonymous point AR mutations are frequently described in this disease, including in the complete phenotype. We present a novel synonymous mutation in the human AR gene (c.1530C > T) in four 46,XY patients from two unrelated families associated with complete androgen insensitivity syndrome (CAIS). The analysis of mRNA from testis showed that synonymous AR mutation changed the natural exon 1 donor splice site, with deletion of the last 92 nucleotides of the AR exon 1 leading to a premature stop codon 12 positions ahead resulting in a truncate AR protein. Linkage analyses suggested a probable founder effect for this mutation. In conclusion, we described the first synonymous AR mutation associated with CATS phenotype, reinforcing the disease-causing role of synonymous mutations (AU)

• Processo FAPESP: 13/02162-8 - Patogênese molecular e caracterização de doenças monogênicas do desenvolvimento: um caminho para a medicina translacional
• Beneficiário: Berenice Bilharinho de Mendonça
• Modalidade de apoio: Auxílio à Pesquisa - Temático
• Processo FAPESP: 14/50137-5 - Caracterização molecular de doenças monogênicas do desenvolvimento por sequenciamento em larga escala
• Beneficiário: Berenice Bilharinho de Mendonça
• Modalidade de apoio: Auxílio à Pesquisa - Programa Equipamentos Multiusuários