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The University of Southampton
Wessex Imprinting GroupInformation for clinicians

Paternal UPD 14 (Wang Syndrome)

Uniparental disomy is the inheritance of both chromosome homologues from one parent with no functional copy from the other.

Since the first reports of and Wang et al and Temple et al in 1991, a well characterised clinical phenotype has emerged for both paternal and maternal uniparental disomy of chromosome 14 (UPD14).

Paternal UPD14 or Wang syndrome is characterised by polyhydramnios, thoracic and abdominal wall defects, growth retardation, severe developmental delay and characteristic dysmorphism.

Imprinted locus at 14q32

There is good evidence that this syndrome is due to aberrant expression of genes at one imprinted locus that exists at 14q32 under the control of a paternally-methylated intergenic differentially-methylated region (IG-DMR). The imprinted genes in this region include the paternally-expressed genes DLK1 (delta, Drosophila homolog-like1) a transmembrane signalling protein and growth regulator homologous to proteins in the Notch/delta pathway and RTL1(retrosposon-like1, PEG11). Maternally expressed genes include numerous C/D box small nucleolar (sno)RNAs and microRNAs, GTL2 (gene trap locus 2), RTL1as and MEG8.

As with other imprinting disorders, it has now been shown that mechanisms that results in functional hemizygosity of 14q32 imprinted genes can cause the clinical phenotypes. It is likely that the paternal UPD14 phenotype will soon be recognised in patients with aberrations at 14q32 as well as paternal UPD14.

Which patients could be tested?

We provide diagnostic testing for all patients with possible UPD 14. Specific features that increase the chance of diagnosis are: marked hypotonia and normal muscle power, early pubertal development, scoliosis, relatively low birth weight at term small hands and feet and developmental delay (although this is not always a feature) and central obesity developing with age. The differential diagnosis includes Prader Willi syndrome.

We would strongly recommend taking blood or DNA from both parents as well as the child, to establish the diagnosis more rapidly.

Details to send with samples

Send details on our request form for imprinting disorders. These include:


When taking samples you should get written consent for the testing - as with any genetic test. You can download a consent form from this site which you might like to use, modify, or translate. We ask you to get consent from the patient/parents to test for ‘imprinting disorders’ rather than just UPD14.

Where should the sample be sent?

Please email us before sending samples

The sample should be sent to:
Dr Deborah Mackay,
Lecturer in Human Genetics
Wessex Regional Genetics Laboratory,
Salisbury Health Care Trust
01722 425048 or 01722429012

And clinical details can be discussed with
Dr Karen Temple
Prof of Medical Genetics
and Honorary Consultant in Clinical Genetics
Academic Unit of Genetic Medicine
Princess Anne Hospital
Coxford Road
SO16 5YA
tel 02380 796625

For more information on genetic testing please look at the genetic testing section on this website.


(1) Wang JCC, Passage MB, Yen PH, Shapiro LJ, Mohandas TK. Uniparental Heterodisomy for Chromosome-14 in A Phenotypically Abnormal Familial Balanced 13/14 Robertsonian Translocation Carrier. American Journal of Human Genetics 1991; 48(6):1069-1074.
(2) Temple IK, Cockwell A, Hassold T, Pettay D, Jacobs P. Maternal uniparental disomy for chromosome 14. J Med Genet 1991; 28(8):511-514.
(3) Sutton VR, Shaffer LG. Search for imprinted regions on chromosome 14: Comparison of maternal and paternal UPD cases with cases of chromosome 14 deletion. American Journal of Medical Genetics 2000; 93(5):381-387.
(4) Wylie AA, Murphy SK, Orton TC, Jirtle RL. Novel imprinted DLK1/GTL2 domain on human chromosome 14 contains motifs that mimic those implicated in IGF2/H19 regulation. Genome Res 2000; 10(11):1711-1718.
(5) Temple IK, Shrubb V, Lever M, Bullman H, Mackay DJ. Isolated imprinting mutation of the DLK1/GTL2 locus associated with a clinical presentation of maternal uniparental disomy of chromosome 14. J Med Genet 2007; 44(10):637-640.
(6) Hosoki K, Ogata T, Kagami M, Tanaka T, Saitoh S. Epimutation (hypomethylation) affecting the chromosome 14q32.2 imprinted region in a girl with upd(14)mat-like phenotype. Eur J Hum Genet 2008.
(7) Buiting K, Kanber D, Martin-Subero JI, Lieb W, Terhal P, Albrecht B et al. Clinical features of maternal uniparental disomy 14 in patients with an epimutation and a deletion of the imprinted DLK1/GTL2 gene cluster. Hum Mutat 2008.

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