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 .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 , 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.
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.
This test is indicated for:
- Confirmation of a clinical/biochemical diagnosis of patUPD6
Isolation using the Perkin Elmer™Chemagen™ Chemagen™ Automated Extraction method or Qiagen™ Puregene kit for DNA extraction is recommended.
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
Submit copies of diagnostic biochemical test results with the sample, if appropriate. Contact the laboratory if further information is needed.