XX males SRY negative: a confirmed cause of infertility

Males with a 46,XX karyotype have in most of the cases the SRY gene translocated to one X chromosome. SRY initiates the cascade leading to testis differentiation having SOX9 gene as first target. We present two XX brothers with normal male differentiation, hypotrophic testes and azoospermia, both negative to SRY. Array-CGH identified an amplification of a 96 kb region, 500 kb upstream to SOX9 promoter. The report of a similar family in which a larger amplification was transmitted through normal fertile XY males, highlights that male differentiation may not be strictly depending on the presence of the SRY gene and that alterations within gene desert regions can significantly reverberate on the phenotype. (By Dr Orsetta Zuffardi, http://jmg.bmj.com/content/early/2011/06/07/jmedgenet-2011-100036.abstract?papetoc )