Examinations of maternal uniparental disomy and epimutations for chromosomes 6, 14, 16 and 20 in Silver-Russell syndrome-like phenotypes

Jana Sachwitz, Getrud Strobl-Wildemann, György Fekete, Laima Ambrozaitytė, Vaidutis Kučinskas, Lukas Soellner, Matthias Begemann, Thomas Eggermann

Silver-Russell syndrome (SRS) is a growth retardation disorder with a very broad molecular and clinical spectrum. Whereas the association of SRS with imprinting disturbances of chromosomes 11p15.5 and 7 is generally accepted, there are controversial discussions on the involvement of other molecular changes. The recent reports on the occurrence of maternal uniparental disomies of chromosomes 6, 16 and 20 (upd(6, 16, 20)mat), as well as 14q32 imprint alterations in patients with SRS phenotypes raise the question on the involvement of these mutations in the etiology of SRS. A cohort of 54 growth retarded patients with SRS features was screened for aberrant methylation patterns of chromsomes 6, 14, 16 and 20. One carrier of a 14q32 epimutation was identified whereas epimutations and maternal UPD for chromosomes 6, 16 and 20 were excluded. Our data and those from the literature confirm that 14q32 disturbances significantly contribute to the mutation spectrum in this cohort. Furthermore, maternal uniparental disomy of chromosomes 6, 16 and 20 can be observed, but are rare. In case they occur they can be regarded as causative for clinical features.