IZKF-CRA03-09Klinefelter Syndrome: Do the Parental Origin and Epigenetic Profile of the Supernumerary X Chromosome Determine Phenotype, Morbidity, Inflammatory Status and Cardiovascular Risk?

This study will elucidate how the parental origin of the X-chromosome influences health status as well as metabolic fate in Klinefelter patients. Epigenetics and transcriptome-research will be directly linked to the metabolic and inflammatory pattern of actual patients to improve care for them. The Klinefelter Syndrome is one of the most common genetic disorders in men. The patients have one supernumerary X-chromosome, which is partly active and disturbs a normal male development. Testosterone deficiency in form of primary hypogonadism is a common feature in these men. Such a condition promotes clinically relevant metabolic patterns related to a pro-inflammatory status and diabetes mellitus type 2 (insulin resis-tance), cardiovascular disease as well as infertility. However, the variety of pathologies is pro-nounced between patients and low testosterone concentrations cannot fully explain the wide scope of pathologies in these men. Some patients become clinically obvious during puberty and adoles-cence, some in their thirties or later and all exhibit a huge variation in phenotype. Switching on and off of specific genes on the X-chromosome is differential, depending on the origin either from the maternal or paternal side. Hence, an influence on the clinical picture is hypothesised. Thus, key targets are clarification of the parental origin of the supernumerary X chromosome and elucidation of methylation and expression profile of pivotal X-chromosomal genes. These will be related to clinically relevant metabolic and inflammatory patterns as well as fertility to identify individual risks as well as treatment strategies for Klinefelter patients.