Uniparental Disomy of Chromosome 6 (UPD6): Methylation Analysis

Condition Description

6q24-relatedtransient neonatal diabetes mellitus (TNDM) is one of the most common causes ofneonatal diabetes, with an estimated incidence of 1 in 400,000 live births [1].TNDM begins in the first six weeks of life and resolves by 18 months of age.Neonates present with severe growth retardation and persistent hyperglycemia. Accordingto one study [2], the average birth weight is 1930 g at 39 weeks gestation, andthe average age at presentation is 7 days. Insulin levels are low orundetectable at presentation, and ketonuria is generally absent. Macroglossiaoccurs in about 1/3 of cases. Umbilical and inguinal hernias have also beenreported. The average length of time on insulin is 111 days. There is noassociation with HLA antigens common in type 1 diabetes. While affected infantsrecover by three months of age, around 50% will develop type 2 diabetes laterin life.

TNDM is causedby overexpression of two imprinted genes at 6q24, PLAGL1 (ZAC) and HYMAI.Both PLAGL1 (ZAC) and HYMAI are expressed from the paternallyinherited chromosome 6. Approximately 35% of TNDM cases are caused by paternaluniparental disomy of chromosome 6.

Methylation-specificPCR is used to assess a differentially methylated region that controlsexpression of PLAGL1 (ZAC) and HYMAI. Both paternal UPD6 and someisolated methylation defects of this imprinted region will be detected by thisanalysis.

References:

1.       Gardner,R.; Mackay, D.; Mungall, A.; Polychronakos, C.; Siebert, R.; Shield, J.;Temple, I.; Robinson, D.: An imprinted locus associated with transient neonataldiabetes mellitus. Human Mol. Gen. 9(4): 589-596, 2000.

2.       Temple, I. and Shield, J.: Transientneonatal diabetes, a disorder of imprinting. J. Med. Genet. 39:872-875, 2002.

Genes (2)

HYMAI, PLAGL1 (ZAC)

Indications

This test is indicated for:

  • Confirmation of a clinical/biochemical diagnosis of patUPD6

Methodology

DNA methylation specific PCR assay targeting the differentially methylated region (DMR) upstream of the PLAGL1 (ZAC) and HYMAI genes on chromosome 6q24 is used to test for paternal uniparental disomy of chromosome 6 (patUPD14). Parental samples are NOT required for patUPD6 analysis, but may be requested to confirm a diagnosis.

Specimen Requirements

Listed below are EGL's preferred sample criteria. For any questions, please call 470.378.2200 and ask to speak with a laboratory genetic counselor (eglgc@egl-eurofins.com).
Submit only 1 of the following specimen types
DNA, Isolated
DNA

Requirements
Microtainer
3µg
Isolation using the Perkin Elmer™Chemagen™ Chemagen™ Automated Extraction method or Qiagen™ Puregene kit for DNA extraction is recommended.
Collection and Shipping
Refrigerate until time of shipment in 100 ng/µL in TE buffer. Ship sample at room temperature with overnight delivery.
Whole Blood (EDTA)
WBP

Requirements
EDTA (Purple Top)
Infants and Young Children (<2 years of age): 2-3 ml
Children > 2 years of age to 10 years old: 3-5 ml
Older Children & Adults: 5-10 ml
Autopsy: 2-3 ml unclotted cord or cardiac blood
Collection and Shipping
Ship sample at room temperature for receipt at EGL within 72 hours of collection. Do not freeze.

Special Instructions

Submit copies of diagnostic biochemical test results with the sample, if appropriate. Contact the laboratory if further information is needed.

How to Order

Requisition Forms