Testing of Buccal Swab DNA Does Not Increase the Detection Rate for Imprinting Control Region 1 Hypomethylation in Silver-Russell Syndrome

Silver-Russell syndrome (SRS) is a congenital imprinting disorder mainly characterized by growth restriction, a triangular shaped face, a relative macrocephaly, and asymmetry of the body and the limbs. In 7%-10% of the patients a maternal uniparental disomy of chromosome 7 (upd(7) mat) can be observed; a hypomethylation of the imprinting control region 1 (ICR1) in 11p15 is present in >38% of patients. Methylation-specific multiplex ligation-dependent probe amplification is a well-established method for the detection of (epi) mutations in 11p15. In routine diagnostics, DNA samples derived from leukocytes are used for this testing approach. We now analyzed buccal smear DNA taken from both cheek sides of 8 carriers of an ICR1 hypomethylation and 25 SRS patients without 11p15 epimutaton or upd(7) mat to check whether (i) the epimutation can be detected in other tissues and (ii) the detection rate can be increased. Indeed, the ICR1 hypomethylation diagnosed in blood cells could be confirmed in the buccal swab DNA of all 11p15 epimutation carriers, but we could not discover any further carriers among the patients without 11p15 epimutation and upd(7) mat in lymphocytes. Thus, the overall detection rate for the 11p15 epimutation could not be increased by including further tissues originating from different germ layers. We rather assume that other-so far unknown-(genetic) factors are contributing to the etiology of SRS that escape the current diagnostic procedures.