Androgen receptor dysfunction as a prevalent manifestation in young male carriers of a FLNA gene mutation

作者：Carrera Garcia Laura^*; Francisco Rivas Crespo Maximiliano; Fernandez Garcia Maria Soledad

来源：American Journal of Medical Genetics, Part A, 2017, 173(6): 1710-1713.

DOI：10.1002/ajmg.a.38230

• androgen insensitivity
• cryptorchidism
• filamin A
• hypogonadism
• periventricular nodular heterotopia

Androgenic actions require the proper signal transmission by the androgen receptor (AR), a nuclear transcription factor. This is initially located in the cell cytoplasm and should translocates to the nucleus to interact with DNA. AR functional impairment causes diverse blockage degrees of androgenic steroid action, known as androgen insensitivity syndromes. Filamin A, a protein coded by the FLNA gene, is a co-activator of various cytoplasmic factors, including AR. The mutational inactivation of the FLNA gene induces insufficiency of translocation and activation of AR. Consequently, it causes a developmental disorder of the male gonad and hypogonadism, similar to those observed in partial androgen insensitivity. We report two brothers carrying a loss-of-function mutation of FNLA with gonadal differentiation disorder and hypospadias. Specific staining for AR shows almost an absolute absence of these receptors in the testicular tissue. This association recommends investigating a possible mutational inactivation of the FLNA gene in patients with cryptorchidism and epididymo-testicular dissociation. The study is especially indicated when the family history, more often that of the mother, is suggestive. Likewise, growth and gonadal development of all male patients carrying this genetic trait should be monitored since childhood.

• 出版日期2017-6