Deborah Mackay (DJGM) leads the Southampton Imprinting Group (SIG) in a broad programme of research on human imprinting disorders, which are congenital disorders affecting the regulation of genes rather than their DNA sequence. The SIG, a multidisciplinary team of laboratory scientists, informaticians and clinical researchers, is delineating the genetic causes, epigenetic features and clinical consequences of imprinting disorders, with two aims: to understand the biology of imprinting, and to improve the lives of patients affected by these disorders.
In 2000 the group identified the locus on chromosome 6q24 for the rare imprinting disorder transient neonatal diabetes (TND, characterised by severe growth restriction and infant diabetes), defined the DNA methylation anomaly that causes it, and developed robust testing for the disorder in affected neonates.
In 2006 the group described individuals with TND who had DNA methylation disturbance not only at the TNDM locus but at other imprinted loci across the genome. This epigenetic phenomenon has come to be known as Multi-locus imprinting disturbance (MLID). The delineation of MLID in affected individuals led DJGM to develop DNA methylation analysis for imprinted loci across the genome, and in the process develop research-based tests for imprinting disorders and MLID, a process that continues to the present.
In 2008 DJGM identified a patient with Temple syndrome (TS14) and a DNA methylation disturbance of the TS14 locus on chromosome 14q32. This enabled the definition of TS14 as an imprinting disorder of chr14. In 2014 the condition was named Temple syndrome after Professor IK Temple, the clinical lead of SIG from 1996 to her retirement. SIG has continued to characterise TS14 and translate its findings into NHS practice. In 2026 the group published a large clinical cohort of patients and a Genereviews article on TS14 diagnosis and management; in 2026 the updated consensus guidelines for Silver-Russell syndrome (SRS) included a section on management of TS14.
In 2008 SIG group showed that mutations in ZFP57 are associated with TND-MLID, implicating ZFP57 in regulation of imprinting during early development. This was the first description of an imprinting disorder caused by a trans-acting genetic change.
In 2015 SIG identified genetic changes in the mothers of individuals with MLID. Beside MLID these changes are associated with a wide range of reproductive outcomes, both viable and nonviable, in offspring of affected mothers. This work has illuminated critical connections between epigenetic marks, maternal reproductive fitness and offspring development and health.
The research project “Imprinting disorders – finding out why” (IDFOW) has run since 2005, as a survey of the genetic, epigenetic and clinical features of imprinting conditions in a UK-based patient cohort. The study continues to show that imprinting disorders are more common and more diverse than classical imprinting disorders would suggest, and reveals new patterns of genotype-phenotype correlation, improves diagnosis, and supports personalised clinical management. The findings of IDFOW are translated into NHS practice; SIG leads an NHS rare disease clinical network (RDCN) on imprinting disorders, and runs the only NHS specialist clinic for imprinting disorders, a service not to our knowledge available anywhere else in the world.
DJGM and other SIG members are widely recognised as global field leaders in imprinting disorders and are in demand for conferences, PAO congresses, clinical training events, specialist teaching, consensus guideline formation, and specialist advice to clinicians and scientists.
