Concomitant Upd(14)mat and Trisomy 14 Mosaicism in a Newborn Detected by Whole Genome Sequencing.

Abstract

Maternal uniparental disomy of chromosome 14, upd(14)mat, leads to Temple syndrome (TS), an imprinting disorder characterized by pre- and postnatal growth retardation, hypotonia, motor delay, joint laxity, and precocious puberty. The occurrence of upd(14)mat is rare, and it may, in even rarer cases, co-occur with trisomy 14 mosaicism. To date, only 11 live-born cases have been reported in the literature. We present a newborn girl with severe hypotonia, global developmental delay, feeding difficulties, dysmorphic features, and cardiac malformations. Using trio whole genome sequencing (WGS) no causative sequence or structural variants were detected. As a chromosomal disorder was suspected the data was further analyzed with a pipeline including analysis of UPD and low-level mosaicism, which revealed upd(14)mat and low level trisomy 14 mosaicism. This study underscores the significance of advanced genetic testing techniques, thorough data interpretation, and expert clinical evaluation in diagnosing rare disorders with complex molecular mechanisms.