Clinical features of maternal uniparental disomy 14 in patients with an epimutation and a deletion of the imprinted DLK1/GTL2 gene cluster

Maternal uniparental disomy 14 [upd(14)mat] is associated with a recognizable phenotype that includes pre‐ and postnatal growth retardation, neonatal hypotonia, feeding problems and precocious puberty. Chromosome 14 contains an imprinted gene cluster, which is regulated by a differentially methylated region (IG‐DMR) between DLK1 and GTL2 . Here we report on four patients with clinical features of upd(14)mat who show a maternal‐only methylation pattern, but biparental inheritance for chromosome 14. In three of the patients loss of paternal methylation appears to be a primary epimutation, whereas the other patient has a paternally derived deletion of −1 Mb that includes the imprinted DLK1‐GTL2 gene cluster. These findings demonstrate that the upd(14)mat phenotype is caused by altered expression of genes within this cluster. Hum Mutat 0, 1–6, 2008. © 2008 Wiley‐Liss, Inc.