SHORT REPORT

Isolated imprinting mutation of the DLK1/GTL2 locus associated with a clinical presentation of maternal uniparental disomy of chromosome 14

I K Temple^1,2, V Shrubb³, M Lever⁴, H Bullman⁴, D J G Mackay^1,4

¹ Division of Human Genetics, University of Southampton, Southampton, Hampshire, UK
² Wessex Genetics Service, Southampton University Hospitals Trust, Southampton, Hampshire, UK
³ Department of Community Child Health, Southampton Community Trust, Southampton, Hampshire, UK
⁴ Wessex Regional Genetics Laboratory, Salisbury Health Care Trust, Salisbury, Hampshire, UK

Correspondence to:
I K Temple
Division of Human Genetics, Princess Anne Hospital, Coxford Road, Southampton, Hants SO31 8DA; ikt{at}soton.ac.uk

The clinical phenotypes of maternal and paternal uniparental disomy of chromosome 14 (UPD14) are attributed to dysregulation of imprinted genes. A large candidate locus exists within 14q32, under the regulation of a paternally methylated intergenic differentially methylated region (IG-DMR). We present a patient with clinical features of maternal UPD14, including growth retardation, hypotonia, scoliosis, small hands and feet, and advanced puberty, who had loss of methylation of the IG-DMR with no evidence of maternal UPD14. This case provides support for the hypothesis that the maternal UPD14 phenotype is due to aberrant gene expression within the imprinted domain at 14q32.

Abbreviations: DLK1, delta, Drosophila homologue-like1; GTL2, gene trap locus 2; IG-DMR, intergenic differentially methylated region; LOM, loss of methylation; MS-PCR, methylation-specific PCR; UPD14, uniparental disomy of chromosome 14

Keywords: UPD14; imprinting; DNA methylation; DLK1; GTL2

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