Blood; extracted DNA is not accepted for Methylation and Copy Number Analysis.
For details about specimen requirements, please refer to: Specimen Type & Requirements (PDF).
- Blood: 5-10 mL in EDTA, 0.5 mL in EDTA (neonate);
- DNA-minimum 10 ug in 100 uL low TE (pH8.0)- for CDKN1C or UPD11 analysis
DNA extracted at an external lab is not accepted for MLPA testing.
For details about specimen requirements, please refer to: Specimen Type and Requirements
If sample shipment >48 hours, ship on ice.
Beckwith-Wiedemann syndrome (BWS) is a growth disorder characterized by a number of features, including large body size, defects in the closure of the abdominal wall during development, and an enlarged tongue. A variety of other features may also present. Patients with BWS also show a significantly increased incidence of childhood tumours, especially Wilms’ tumor.
In 85 per cent of cases, there is no family history of BWS. However, in approximately 15 per cent of cases, BWS is transmitted from one generation to the next. In these families, BWS is inherited in an autosomal dominant fashion, usually through the mother. There is no way to predict which or how many of the features characteristic of BWS will be present in an individual with the mutation.
There are a number of genetic changes that cause BWS. To date, all of these occur on chromosome 11 at 11p15.
Methylation at KvDMR and H19
Methylation abnormalities at differentially methylated regions (DMR) in the 11p15 region have been shown to cause BWS. KCNQ1OT1 is a maternally imprinted non-coding antisense transcript. The 5’ region of KCNQ1OT1 (KvDMR) is differentially methylated. Normally, the maternally derived chromosome is methylated, whereas the paternally derived chromosome is unmethylated. Loss of maternal methylation at KvDMR is observed in 50- 60 per cent of individuals with BWS. H19 is a paternally imprinted gene encoding a biologically active non-coding transcript that may function as a tumour suppressor. Normally, the paternally derived chromosome is methylated and the maternally derived chromosome is unmethylated. Gain of maternal methylation at H19 is observed in ~5 per cent of BWS cases. For molecular analysis, the methylation status at KvDMR and H19 is measured. Individuals with UPD can be distinguished from individuals with abnormal methylation of either KvDMR or H19 since those with UPD have methylation abnormalities at both KvDMR and H19. If the methylation results are normal at both KvDMR and H19, this result indicates normal biparental contributions in the tissue sample tested (N.B. see Sensitivity of the Test below).
Approximately 10-20 per cent of BWS cases have received two copies of the 11p15 region from their father and none from their mother, which is called paternal uniparental disomy (patUPD). Paternal UPD patients have an imbalance of gene expression in the BWS critical region. Dosage analysis of paternal and maternal genes in the BWS critical region can be used to detect UPD.
Patients with BWS may also have mutations in the CDKN1C (p57) gene. The CDKN1C gene is a member of the cyclin-dependent kinase inhibitor family, which acts to negatively regulate cell proliferation. Mutations in the CDKN1C gene have been reported in approximately 5-10 per cent of BWS cases with no known family history and in approximately 40 per cent of cases in inherited autosomal dominant families.
See related information sheet: Beckwith-Wiedemann Syndrome
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