Search for altered imprinting marks in Mayer-Rokitansky-Küster-Hauser patients.

Background: Mayer-Rokitansky-Küster-Hauser syndrome (MRKH) is the second most common cause of primary amenorrhea and characterized by absence of the uterus and the upper part of the vagina. The etiology of MRKH is mainly unknown but a contribution of genomic alterations is probable. A molecular disturbance so far neglected in MRKH research is aberrant methylation at imprinted loci. In fact, MRKH has been reported in patients with the imprinting disorder Silver-Russell syndrome.

Methods: We report on a rare patient with MRKH and SRS due to an ICR1 hypomethylation in 11p15.5. On the basis of this observation we screened a large cohort of MRKH patients (n > 100) for aberrant methylation at nine imprinted loci.

Results: We failed to detect any epimutation, thus we conclude that imprinting defects at least at the currently known disease-relevant imprinted loci do not contribute to the isolated MRKH phenotype. However, it cannot be excluded that altered methylation marks at other loci are involved in the etiology of MRKH.

Conclusion: The molecular basis for MRKH remains unclear in the majority of patients, but future studies on the association between MRKH and ICR1 hypomethylation/SRS will to enlighten the role of epigenetics in the etiology of MRKH.