Uniparental disomy: clinical indications for testing in growth retardation

Abstract.

Growth is a complex process which is in part genetically determined. Among other genetic causes, uniparental disomy (UPD), the exceptional inheritance of two homologous chromosomes from only one parent, may occasionally be detected. Recent insights have revealed that the molecular basis for the clinical features of UPD are specific human genes that are only monoallelically active, depending on whether they are located on the paternal or maternal chromosome. UPD will lead to an imbalanced expression of these imprinted genes and cause abnormal development. Meanwhile, specific syndromes have been found to be associated with UPD, these include Prader-Willi syndrome (maternal UPD15/mUPD15), Angelman syndrome (paternal UPD15/pUPD15), (transient) neonatal diabetes mellitus (pUPD6), Silver-Russell syndrome (mUPD7), Beckwith-Wiedemann syndrome (pUPD11) and the mUPD14 syndrome. Among other features, most of these syndromes are also characterised by growth restriction. Additionally, UPDs of further chromosomes have been described in growth restricted patients without additional phenotypic abnormalities; however, a conclusive association between the UPD and the clinical features remains to be investigated. Conclusion: in this review we propose a set of reasons for testing of specific uniparental disomies other than 15 in growth restricted patients.