Where does extra X in klinefelter syndrome come from?

Abstract

It has been reported that the incidence of sperms with disomic XY is higher in the testis tissue smear of KS patients and these sperms are the cause of KS. However some papers report the maternal origin. So we performed this study to investigate the origin of extra X in Klinefelter Syndrome (KS). Cytogenetic analysis in KS patients and their parents. Blood samples from 29 KS patients were used for X-chromosome short tandem repeats (STR) analysis. The STR analysis also included data of the parents of the KS patients (24: both parents, 5: mother only, 0: father only) from January 2015 to March 2019. This study was conducted with the informed consent of all participating patients and approved by The Institutional Review Boards of the Saint Mother Obstetrics and Gynecology Clinic and adhered to JCMJER criteria UMIN Clinical Trial Registry was UMIN000024542. Blood samples of 29 KS patients and one or both of their parents were used to determine the origin of the extra X chromosome using X-chromosome haplotype markers (short tandem repeats of 12 loci), according to the method by Shrivastava et al. With DNA extracted from the samples, multiplexed PCR amplifications of the 12 X-STR loci and AMELOGENIN were conducted using an Investigator Argus X-12 QS Kit (Quigen, Germany). The data obtained was analyzed with GeneMapper ID software. X-chromosomal STR DNA profiles were compared among KS patient and their parents. In 13 of the 29 KS patients, both two X chromosomes were maternal origin, showing that an extra X chromosome was left in an oocyte as a result of chromosomal non-disjunction at the 1st (4/13) or 2nd (9/13) meiotic division. In 15 patients, X-chromosomes were inherited from parents, suggesting that fertilization of XY-sperm is the cause of KS.Table 1The result of X-chromosome STR analysis (a case of maternal origin extra-X)Patient no. 09KYMarkerDXS10148DXS10135DXS8378DXS10079DXS10074DXS7132Father20221018, 211716Mother20, 22.121, 221017, 18, 2016, 1814, 15Patient22.1221018, 201814MarkerHPRTBDXS10101DXS10103DXS10134DXS10146DXS7423Father1231.2183524, 40.214Mother13, 1429, 31.217, 1936, 37.326, 3215, 16Patient1429, 31.217, 1936, 37.326, 3215, 16 Open table in a new tab Although the sample number applied for X-chromosomal STR DNA profiling is not enough, the present data may indicate that contribution of XX oocyte to the production of XXY embryos is greater than XY sperm. Namely, a XX oocyte penetration by a Y sperm is the main cause of KS. Cytogenetic analysis with smear of testicular cell mixture that was used in the studies may overestimate chromosomal abnormality.