SRY-negative 46,XX male with normal genitals, complete masculinization and infertility

Abstract

XX maleness is a rare syndrome with a frequency of 1 in 20,000-25,000 males. XX males exist in different clinical categories with ambiguous genitalia or partially to fully mature male genitalia, in combination with complete or incomplete masculinization. In this study, we report a case of SRY-negative XX male with complete masculinization but infertility. The patient had fully mature male genitalia with descended but small testes and no signs of undervirilization. PCR analysis for SRY, ZFY, Amelogenin, AZFa, AZFb, AZFc genes, a pair of primers from heterochromatic region and six Y-STRs showed the absence of any Y-chromosome-derived material. Absence of SRY gene was confirmed by three independent PCRs for each of two sets of primers covering an increasing length of the gene. Sequence analysis of the coding regions of SOX9 and DAX1 genes did not reveal any mutation. Real-time PCR assay revealed normal copy number for SOX9 gene. Microsatellite analysis showed no evidence of 17q (SOX9 gene) or 22q duplication. Genotyping with X-STRs ruled out the possibility of any deletion on X chromosome. Development of the male phenotype in the absence of SRY probably resulted from the loss of function mutation in some unknown sex-determining gene, which normally inhibits the male pathway, or from a gain of function mutation in a gene downstream to SRY in male pathway.

Clinical, cytogenetic, and molecular analysis with 46,XX male sex reversal syndrome: case reports

“…Any mutation leading to increased expression of either gene could lead to female-to-male sex reversal in 46,XX SRYnegative individuals [22,23]. Huang et al reported a 46,XX sex reversal individual with duplication of chromosome 17q including SOX9 [24], which suggested that overexpression of male determining genes could trigger testis determination in the absence of SRY.…”

Primary male infertility in Izmir/Turkey: a cytogenetic and molecular study of 187 infertile Turkish patients

“…Majority of XX males carry SRY gene translocated to the X chromosome, as in our case, due to a recombination between X and Y chromosome. These patients are sterile men but have normal genitalia [26].…”

Infertility caused by male partners with genetic defects in Sichuan Province of China

“…SRS can be divided into 46, XX male SRS and 46, XY female SRS. In humans, XX maleness occurs with an incidence of approximately 1 in every 20,000-30,000 male births (Ergun-Longmire et al, 2005;Rajender et al, 2006;Vorona et al, 2007). The incidence in the infertile men in our study was 1.57% above average.…”

“…The pathogenesis of this rare karyotype is complicated and may result from the nondisjunction of primary spermatocyte in meiosis I followed by the nondisjunction of sister chromatids in meiosis II or from the combination of an aneuploidy gamete derived from nondisjunction of secondary spermatocytes and maternal secondary oocytes (Kleiman et al, 1999). Sex reversal syndrome (SRS) is a disease of gonadal sex and chromosomal sex inconsistency (Rajender et al, 2006). SRS can be divided into 46, XX male SRS and 46, XY female SRS.…”