Endocrine Abstracts

Klinefelter syndrome (KS) was first described in 1942 and the cause for the syndrome was identified as a supernumerary X chromosome resulting in the karyotype 47,XXY. 80–90% of KS cases bear this karyotype, whereas the remaining exhibit (in decreasing frequency) varying mosaicism (e.g. 47,XXY/46,XY), carry additional sex chromosomes (48,XXXY; 48,XXYY; 49,XXXXY) or structurally abnormal X chromosomes. The prevalence of KS is up to 1 in 500 boys, and it is the most common chromosomal aberration in men (0.1–0.2% of the male population). Although KS has been extensively studied in the last decades, the pathophysiology, i.e. the link between the supernumerary X and the phenotype, largely remains unclear and the variability unexplained. Apart from normal interindividual genetic variation, several genetic mechanisms may be involved in the variability of the phenotype: in principal, the parental origin of the X chromosome and gene-dosage effects (GDE) in conjunction with (possibly skewed) X chromosome inactivation. In order to clarify the role of GDE in KS, we analyzed 63 patients with non-mosaic karyotype by Quantitative Real Time PCR, comparing the results of expression of 12 genes (ASMTL, CSF2RA, DHRSXY, DXYS155E, MIC2, P2RY8, PGPL, PR48, SLC25A6, SPRY3, SYBL1, ZBED1) located in the pseudoautosomal region1 and 2 (PAR1 and 2) of X-chromosome with the results obtained from 38 XY fertile male, 35 XX fertile female and 4 non-mosaic Turner syndrome patients. The obtained results showed a differential expression of PAR1 and 2 genes between KS and controls (male and female), and for many of these genes this is the first description of their expression behaviour in male and KS. Finally, a genotype–phenotype correlation for the genes whose function is known was attempted, disclosing appealing pathogenetic hypothesis.

Declaration of interest: The authors declare that there is no conflict of interest that could be perceived as prejudicing the impartiality of the research project.

Funding: This research did not receive any specific grant from any funding agency in the public, commercial or not-for-profit sector.