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|Performed by||Shodair Children's Hospital Genetics lab|
|Method||Upon Southern hybridization to a BamHI/ NotI digest of genomic DNA, a 370 bp LIT1 /
KCNQ1OT1 probe (containing EST 592241) detects two bands for a normal biparental pattern
(Lee et al., PNAS, 1999, 96:5203-8).
|Collection Instructions||Complete a Shodair test request and send with sample to the lab for testing. Click here for form|
|Container type||Lavender top|
|Amount to Collect||5 mL blood|
|Sample type||EDTA Whole blood, Cultured amniocytes, cultured chorionic villi|
|UCSF Rejection Criteria||Blood collected in heparin. Deficient confluency in cultured cell flasks.|
|Processing notes||Do not centrifuge. Do not freeze. Refrigerate sample|
|Synonyms||BWS; Overgrowth Disorder; Imprinted disorder; macroglossia; LIT1|
|Turn around times||Results are reported within 3 weeks or less of receipt of sample.
Note: Prenatal turnaround time is targeted at ≤ 2 weeks.
|Additional information||Beckwith-Wiedemann Syndrome (BWS) has an estimated incidence of 1 in 13, 700. Approximately 85% of BWS cases are sporadic and 15% are hereditary. BWS is an overgrowth disorder usually detected at birth and is associated with increased risk of childhood cancer such as Wilm's tumor. The diagnosis of BWS is primarily based on clinical findings although cytogenetic abnormalities involving chromosome 11 can be detected in 1% of cases.
Hypomethylation abnormalities at the maternally DMR2 imprinted locus are present in 50% of BWS cases, whereas hypermethylation at the DMR1 locus is associated with BWS in 2-7% of cases only. Other causes of BWS are paternal uniparental disomy for chromosome 11, which occur in 10-20% of BWS cases. Mutations in the CDKN1C gene (also called p57Kip2) are also associated with BWS in 40% of inherited cases.
Assisted Reproductive Technology (ART) has been reported to result in elevated rates of BWS and thus fetuses conceived by ART are often tested for methylation abnormalities such as in BWS, Prader-Willi and Angelman syndromes.
This assay evaluates the methylation status of the LIT1 locus (also called KCNQ1OT1) and is aimed at the detection of parent-specific methylation of the BWS critical region. Hypomethylation of LIT1 is the most common DNA methylation abnormality causing BWS and accounts for 50-60% of BWS cases. H19 hypermethylation, which accounts for 5% of BWS, is not detected by this assay.
Somatic mosaicism for 11p15.5 paternal uniparental disomy has been reported in approximately 20% of affected individuals with BWS. Low-level mosaicism may explain borderline or negative results in cases with a strong clinical suspicion. Testing a second specimen from a different source may increase the diagnostic sensitivity.
NOTE: The methylation index generated at the LIT1 locus from chorionic villi specimens may not accurately reflect a definitive methylation pattern as chorionic villi are at an early developmental stage and might not have reached an established methylation pattern throughout the genome.
This test was developed and its performance characteristics determined by the Clinical Laboratories at the Medical Center at UC San Francisco. It has not been cleared or approved by the U.S. Food and Drug Administration.
|Last Updated||5/22/2013 2:09:16 PM|
If you have additional questions regarding this test, please call: 415-353-1667