Quantitative DNA methylation analysis improves epigenotype-phenotype correlations in Beckwith-Wiedemann syndrome

Figures & data

Table 1. Clinical features and methylation values of ICR1 and ICR2 in the postnatal cases

Figure 1. Distribution of ICR1 and ICR2 methylation values in the control population (A) and postnatal BWS cases (B). Vertical (ICR1) and horizontal (ICR2) lines define the threshold levels of normal methylation values. The cases (▲) with mild ICR1 hypermethylation associated with abdominal wall defects (umbilical hernia or diastasis recti), but not with omphalocele, are encircled by a solid line. The cases (▲) with severe ICR1 hypermethylation associated with macroglossia, macrosomia, and visceromegaly are encircled by a dotted line. Cases with ICR2 hypomethylation (♦). Cases with both ICR1 and ICR2 methylation anomalies, indicating UPD ()

Table 2. : Percentage levels of ICR1 and ICR2 methylation in controls and cases

Population (number of subjects)	Mean methylation, % (range)
	ICR1	ICR2
Postnatal analyses
Controls (103)	46 (40–52)	45 (39–50)
Cases (41)
7	71 (57–86)*	47 (41–50)
4	49 (46–53)	18 (6–26)*
8	59 (55–68)*	34 (31–36)*
22	48 (44–52)	45 (42–49)
Prenatal analyses
Amniotic fluid controls (16)	44 (38–48)	42 (37–47)
Cases (3)
1	48	30*
2	46 (44–47)	41 (37–45)

* Abnormal methylation.

Figure 2. Frequencies of the different methylation defects (ICR1 hypermethylation, ICR2 hypomethylation, and both ICR1 and ICR2 methylation anomalies) in the cohort of the current study (left) and in cohorts of previous studies (http://www.ncbi.nlm.nih.gov/books/NBK1394/#bws.Summary) (right).

Table 3. Descriptions of the three prenatal cases with suspected BWS

Sample ID	W.g. of AF sampling	Conception method	Features detected on ultrasound	Exitus	Karyotype	Clinical outcome	Methylation level (%) ICR1 ICR2
F1	18th+4	Spontaneous	Omphalocele	Abortion at 20th w.g.	46,XX	Omphalocele, visceromegaly, macroglossia, and peculiar craniofacial features	48	30
F2	16th+1	Spontaneous	Omphalocele	Abortion at 20th w.g.	46,XY	No additional signs of BWS	47	45
F3	16th+1	Intra-cytoplasmic injection	Bi-amniotic bi-chorial twin pregnancy Omphalocele and a growth delay in the female fetus	Twins born at 37th w.g.	46,XX (fetus with omphalocele) 46,XY (normal fetus)	Omphalocele was not present at birth	44	37

w.g, week of gestation

Figure 3. Autopsy of prenatal case F1. Hypertrophy of the labia majora (A), macroglossia (B), ear anomalies (C), visceromegaly with hepatomegaly, nephromegaly, and ovarian hypertrophy (D and E), and adrenocortical cytomegaly (F).