Methylation pattern and copy number analysis by MS-MLPA of patients with recurrent t(4;11). (A) Pedigrees illustrating the parental origin of the duplicated 11p material if the balanced translocation is present in the father (left), or the mother (right). (Blue) Paternal inheritance; (pink) maternal inheritance. (B) Schematic representation of the imprinted region at 11p15. The imprinted 11p15 region consists of two independent domains that are regulated by differentially methylated regions (DMR). The telomeric DMR1 is paternally methylated and regulates reciprocal expression of H19 and IGF2 genes. The centromeric DMR2 is maternally methylated and regulates expression of imprinted genes in this region including CDKN1C, KCNQ1OT1, and KCNQ1. CH3 represents the methylated allele. (C) Partial profile of MS-MLPA HhaI digestion/ligation products for patients 2, 4, and 4U (blue) compared to normal control (red). Increased peak intensities of IGF2 and KCNQ1 in patients 2, 4, and 4U indicate duplication of the 11p15 region. Gain of methylation in the HhaI sensitive DMR2 was detected in patients 2 and 4, whereas gain of methylation in the HhaI sensitive DMR1 was detected in patient 4U. The results demonstrated that maternal inheritance (M) of the duplicated 11p15 region in patients 2 and 4 and paternal inheritance (P) of the duplicated 11p15 region in patient 4U.
