An Infertility SRY-Negative 46, XX Male Detected by Quantitative Fluorescent Polymerase Chain Reaction

Abstract

Taking a frequency of 1 in 20,000-25,000 males, De la Chappelle syndrome (46, XX male) is a rare syndrome which exists in different clinical categories with ambiguous genitalia or partially to fully mature male genitalia, in combination with complete or incomplete masculinization. A case of SRY-negative XX male is reported with complete masculinization but with infertility. The patient was mature enough to have full genitalia with descended but small testes and no signs of undervirilization. There were 14 markers in the quantitative fluorescent polymerase chain reaction (QF-PCR): amelogenin gene, presented on X and Y chromosomes allows for the determination of the Y/X ratio (AMEL marker), TAF9B gene presented on chromosomes X and 3 permits the determination of X/chromosome 3 ratio (TAF9B marker or T3 marker), ten non-polymorphic Y-specific markers (SRY, sY84 and sY86 in AZFa region, sY127 and sY134 in AZFb region, sY254, sY255, sY1191, sY1192 and sY1291 in AZFc region), and co-amplification of DAZ/DAZL and CDY2/CDY1 fragments that permit determination of the DAZ, CDY1 and CDY2 gene copy number. The study resulted that there were only two peaks of markers: AMELX/Y marker produced a peak area ratio of 1:0 and T3 with the ratio of 2:2, indicating the presence of two X chromosomes in this case. The absence of the Y chromosome was confirmed when repeating peripheral blood culture for chromosome: there are 46 chromosomes with XX constitution. The first reported case in Mekong Delta, Vietnam is reported of a SRY-negative 46, XX male with normal male phenotype and infertility.

A case reported with 46, XX testicular disorders of sexual development and its possible association with dysembryoplastic neuroepithelial tumour

“…On the other hand, the SRY negative DSDs commonly have genital anomalies which can lead to diagnosis right after birth or they may present later with gynecomastia, short stature, undescended testes or hypospadias. 7,10 However, cases have been reported of SRY negative 46, XX males with normal sexual development as well. 2,10 The pathogenesis behind this SRY negative testicular DSD might be because of mosaicism of SRY gene in gonads.…”

“…7,10 However, cases have been reported of SRY negative 46, XX males with normal sexual development as well. 2,10 The pathogenesis behind this SRY negative testicular DSD might be because of mosaicism of SRY gene in gonads. 11 Another mechanism proposed is SOX9 gene which works with SRY gene for differentiation of gonads into the testes and its over expression can lead to testicular development even in the absence of SRY and microdeletions/duplication in SOX3 have also been linked with SRY negative XX males.…”