Table 1

DNA-methylation analysis of imprinted gene loci

II-3II-4III-1III-2III-3
NameMethylated allelePhenotypeChromosome regionMethodpbpbmupblym clfib clbsCVSmu
ARHI/DIRAS3M 1p31.3MSPna
BS-PS↔ (54)↑ (67)↓ (40)↓ (13)nananana↔ (42)
PLAGL1MTNDM6q24.2MSPna↓/↔na
BS-PS↔ (31)↔ (37)↓ (6)↓ (9)↓ (11)nanana↓ (25)
GRB10MSRS7p12.2MSPnana
BS-PS↔ (26)↔ (22)↓ (7)↓ (11)↓ (12)nanana↔ (37)
MESTM 7q32.2MSP↓/↔na
BS-PS↔ (29)n.d.↓ (6)↓ (18)nananana↔ (38)
KCNQ1OT1MBWS11p15.5MLPA↔ (∼50)↔ (∼50)↓ (5–10)↓ (10–15)↓ (10–15)↓(∼25)↓ (15–20)↓(∼25)na
KCNQ1PBS-PS↔ (20)↔ (16)↓ (10)↓ (7)↓ (7)nanana↓ (7)
IGF2PSRSBS-PS↔ (52)↔ (45)↔ (45)↓ (25)↓ (19)nanana↔ (43)
H19MLPA↔ (∼50)↔ (∼50)↔ (∼50)↓ (∼10)↓ (10–15)↓(∼25)↓ (20–25)↔ (∼50)na
H19_6CTCFBS-PS↔ (23)↔ (31)↔ (28)↓ (5)↓ (5)nanana↔ (19)
H19_3CTCFBS-PS↔ (19)↔ (15)↔ (22)↓ (9)nanananana
RB1M13q14.2MSPnanananana
MEG3PTS14q32BS-PS↔ (41)↔ (42)↓ (6)↓ (19)nananana↓ (24)
MEG3_aMSPnanana
MEG3_bMSPnana
IG-DMR DLK1/GTL2MSP/SeQMAna
SNRPNMAS15q11.2MLPA↔ (∼50)↔ (∼50)↔ (∼50)↓ (20–25)↓ (∼15)↓ (10–20)↓ (∼30)↔ (∼50)na
BS-PS↔ (38)↔ (39)↔ (35)↓(17)↓ (17)nanana↔ (38)
NDNMLPA↔ (∼50)↔ (∼50)↔ (∼50)↓(∼20)↓ (∼15)↓(∼20)↔ (∼35*)na
BS-PS↔ (47)↔ (41)na↓ (37)↔ (40)nanana↓ (29)
PEG3M 19q13MSPnana
BS-PS↔ (33)↔ (38)↓ (5)↓ (23)↓ (24)nanana↔ (33)
GNASMPHP1b20q13.2MSPnana
NESPASMSPnanana
NESPPMSPnana
  • *NDN is always hypomethylated in CVS.

  • DNA-methylation of 21 imprinted loci of 17 known imprinted regions was investigated by different methods in nine samples of the parents (II-3, II-4) and their three children (III-1, III-2, III-3). The results are summarised with respect to the analysed region and which known syndromes/phenotypes are affected if the genes are hypomethylated (column 3). All values are rounded up. The methylation value per locus is given in the parenthesis.

  • AS, Angelman syndrome; bs, buccal swab; BS-PS, bisulfite-pyrosequencing; BWS, Beckwith–Wiedemann syndrome; chr region, chromosomal region of the imprinted loci; CVS, chorionic villi; fib cl, fibroblast cell line; lym cl, lymphoblastoid cell line; M, maternal; methyl allele, methylated allele; MLPA, multiplex ligation-dependent probe amplification; MSP, methylation-specific PCR; mu, muscle; P, paternal; pb, peripheral blood; PHP1b, Pseudohypoparathyroidism type 1b; SeQMA, sequence-based quantitative methylation analyses; SRS, Silver–Russell syndrome; TNDM, transient neonatal diabetes mellitus; TS, Temple syndrome; ↔, normally methylated; ↑, hypermethylated; ↓, hypomethylated; ▾, unmethylated; ↓/↔, marginal hypomethylated; na, not analysed.