Structural analysis of the impact of a novel androgen receptor gene mutation in two adult patients with mild androgen insensitivity syndrome.
Andrologia
; 53(1): e13865, 2021 Feb.
Article
em En
| MEDLINE
| ID: mdl-33108824
ABSTRACT
Androgen receptor gene (AR) mutations are responsible for androgen insensitivity syndrome (AIS) presenting with a clinical phenotype that ranges from gynaecomastia and/ or infertility in mild AIS (MAIS) to complete testicular feminisation in complete AIS. We report a novel AR gene mutation in two unrelated adult patients with MAIS and we studied its functional impact using 3D modelling. Patient 1, referred for infertility, presented with gynaecomastia, mild hypospadias and bilateral testicular hypotrophy contrasting with high testosterone levels, an elevated FSH, an elevated androgen sensitivity index (ASI) and oligoasthenoteratospermia. In vitro fertilisation and intracytoplasmic sperm injection resulted in a successful twin pregnancy. Patient 2 referred for a decrease in athletic performance had surgically treated gynaecomastia, oligoasthenospermia, high testosterone levels and an elevated ASI. Despite his impaired spermogram, he fathered two children without assisted reproductive technology. AR gene sequencing in the two patients revealed a common novel missense mutation, Ala699Thr, in exon 4 within the ligand-binding domain. 3D modelling studies showed that this mutation may impact dimer stability upon ligand binding or may affect allosteric changes upon dimerisation. This study illustrates the value of structural analysis for the functional study of mutations and expands the database of AR gene mutations.
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Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Síndrome de Resistência a Andrógenos
Tipo de estudo:
Prognostic_studies
Limite:
Adult
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Child
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Female
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Humans
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Male
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Pregnancy
Idioma:
En
Revista:
Andrologia
Ano de publicação:
2021
Tipo de documento:
Article
País de afiliação:
França