AbstractBackgroundA male individual with a karyotype of 46,XX is very rare. We explored the genetic aetiology of an infertility male with a kayrotype of 46,XX andSRYnegative.MethodsThe peripheral blood sample was collected from the patient and subjected to a few genetic testing, including chromosomal karyotyping, azoospermia factor (AZF) deletion, short tandem repeat (STR) analysis forAMELX, AMELYandSRY, fluorescence in situ hybridization (FISH) with specific probes for CSP 18/CSP X/CSP Y/SRY, chromosomal microarray analysis (CMA) for genomic copy number variations(CNVs), whole-genome analysis(WGA) for genomic SNV&InDel mutation, and X chromosome inactivation (XCI) analysis.ResultsThe patient had a karyotype of 46,XX.AZFanalysis showed that he missed theAZFregion (including a, b and c) andSRYgene. STR assay revealed he possessed theAMELXin the X chromosome, but he had no theAMELYandSRYin the Y chromosome. FISH analysis with CSP X/CSP Y/SRYshowed only two X centromeric signals, but none Y chromosome andSRY. The above results of the karyotype, FISH and STR analysis did not suggest a Y chromosome chimerism existed in the patient's peripheral blood. The result of the CMA indicated a heterozygous deletion with an approximate size of 867 kb in Xq27.1 (hg19: chrX: 138,612,879–139,480,163 bp), located at 104 kb downstream ofSOX3gene, includingF9,CXorf66,MCF2andATP11C. WGA also displayed the above deletion fragment but did not present known pathogenic or likely pathogenic SNV&InDel mutation responsible for sex determination and development. XCI assay showed that he had about 75% of the X chromosome inactivated.ConclusionsAlthough the pathogenicity of 46,XX male patients withSRYnegative remains unclear,SOX3expression of the acquired function may be associated with partial testis differentiation of these patients. Therefore, the CNVs analysis of theSOX3gene and its regulatory region should be performed routinely for these patients.
