Molecular and clinical analyses of two patients with UPD(16)mat detected by screening 94 patients with Silver-Russell syndrome phenotype of unknown aetiology

background recently, a patient with maternal uniparental disomy of chromosome 16 (UpD(16)mat) presenting with Silver-russell syndrome (SrS) phenotype was reported. SrS is characterised by growth failure and dysmorphic features. Objective to clarify the prevalence of UpD(16)mat in aetiology-unknown patients with SrS phenotype and phenotypic differences between UpD(16)mat and SrS. Methods We studied 94 patients with SrS phenotype of unknown aetiology. Sixty-three satisfied the Netchine-harbison clinical scoring system (Nh-CSS) criteria, and 25 out of 63 patients showed both protruding forehead and relative macrocephaly (clinical SrS). the remaining 31 patients met only three Nh-CSS criteria, but were clinically suspected as having SrS. to detect UpD(16)mat, we performed methylation analysis for the ZNF597:tSS-differentially methylated region (DMr) on chromosome 16 and subsequently performed microsatellite, SNp array and exome analyses in the patients with hypomethylated ZNF597:tSS-DMr. results We identified two patients (2.1%) with a mixture of maternal isodisomy and heterodisomy of chromosome 16 in 94 aetiology-unknown patients with SrS phenotype. Both patients exhibited preterm birth and prenatal and postnatal growth failure. the male patient had ventricular septal defect and hypospadias. Whole-exome sequencing detected no gene mutations related to their phenotypes. Conclusion We suggest considering genetic testing for UpD(16)mat in SrS phenotypic patients without known aetiology.