Clinical and Molecular Presentation of a Patient with Paternal Uniparental Isodisomy of Chromosome 16

Uniparental disomies (UPDs) are among the causes of imprinting disorders. Specific phenotypes of most causative UPDs have been described. Here, we describe the case of a 2-year-old female patient who presented a syndromic phenotype. Chromosomal microarray analysis revealed UPD of the whole chromosome 16. Microsatellite analysis demonstrated paternal origin of the UPD and its isodisomic pattern (UPiD (16) pat). Mosaic trisomy 16 was not detected using the FISH method. Whole-exome sequencing revealed no pathogenetic genetic variants sufficient to explain the syndromic phenotype nor unmasked pathogenic recessive genetic variants on chromosome 16. Whole-genome trio DNA sequencing revealed no additional candidate pathogenic genetic variants to those detected by whole-exome sequencing, including miRNAs and lncRNAs. Imprinting disorders at 6q24.2, 7p12.2, 7q32.2, 11p15.5, 14q32.2, 15q11.2, and 20q13.32, as well as multilocus imprinting disturbances (MLIDs), were excluded by Methylation-Specific Multiplex Ligation-Dependent Probe Amplification (MS-MLPA). At the same time, we detected abnormal hypermethylation of the ZNF597 transcription start site differentially methylated region (ZNF597:TSS-DMR), accompanied by hypomethylation of the neighbouring ZNF597:3′ DMR. Both DMRs were normally imprinted, and the DNA alterations in our patient with UPD (16) pat are opposite to those previously described for maternal uniparental disomy (UPD (16) mat). To date, several cases of UPD (16) pat have been reported. Our case report describes the syndromic phenotype of a patient with paternal uniparental disomy of chromosome 16 in contrast to the previously described patients with a normal phenotype or with abnormal phenotypes caused by acquired homozygosity of pathogenic variants at autosomal recessive genes located on this chromosome. Reporting such observations will help systematize data on the phenotypes of imprinting disorders on chromosome 16.