Epimutation at human chromosome 14q32.2 in a boy with a upd(14)mat‐like clinical phenotype

Abstract

Recently, three reports described deletions and epimutations affecting the imprinted region at chromosome 14q32.2 in individuals with a phenotype typical for maternal uniparental disomy of chromosome 14 [upd(14)mat]. In this study, we describe another patient with upd(14)mat-like phenotype including low birth weight, neonatal feeding problems, muscular hypotonia, motor and developmental delay, small hands and feet, and truncal obesity. Conventional cytogenetic analyses, fluorescence in situ hybridization subtelomere screening, multiplex ligation-dependent probe amplification analysis of common microdeletion and microduplication syndromes, and methylation analysis of SNRPN all gave normal results. Methylation analysis at 14q32.2 revealed a gross hypomethylation of the differentially methylated regions (intergenic DMR and MEG3-DMR). Further molecular studies excluded full or segmental upd(14)mat as well as a microdeletion within this region. Evidently, the upd(14)mat-like clinical phenotype is caused by an epimutation at 14q32.2. The clinical and molecular features of this novel case are discussed with respect to the recently published cases.