Maternal Uniparental Disomy 14 Syndrome Demonstrates Prader-Willi Syndrome-Like Phenotype

Objective

To delineate the significance of maternal uniparental disomy 14 (upd(14)mat) and related disorders in patients with a Prader-Willi syndrome (PWS)–like phenotype.

Study design

We examined 78 patients with PWS-like phenotype who lacked molecular defects for PWS. The MEG3 methylation test followed by microsatellite polymorphism analysis of chromosome 14 was performed to detect upd(14)mat or other related abnormalities affecting the 14q32.2-imprinted region.

Results

We identified 4 patients with upd(14)mat and 1 patient with an epimutation in the 14q32.2 imprinted region. Of the 4 patients with upd(14)mat, 3 had full upd(14)mat and 1 was mosaic.

Conclusions

Upd(14)mat and epimutation of 14q32.2 represent clinically discernible phenotypes and should be designated “upd(14)mat syndrome.” This syndrome demonstrates a PWS-like phenotype particularly during infancy. The MEG3 methylation test can detect upd(14)mat syndrome defects and should therefore be performed for all undiagnosed infants with hypotonia.

PWS, Prader-Willi syndrome, Upd(14)mat, Maternal uniparental disomy 14, Upd(14)pat, Paternal uniparental disomy 14