RT Journal Article SR Electronic T1 Paternal uniparental disomy of chromosome 19 in a pair of monochorionic diamniotic twins with dysmorphic features and developmental delay JF Journal of Medical Genetics JO J Med Genet FD BMJ Publishing Group Ltd SP 847 OP 852 DO 10.1136/jmedgenet-2018-105328 VO 55 IS 12 A1 Kit San Yeung A1 Matthew Sai Pong Ho A1 So Lun Lee A1 Anita Sik Yau Kan A1 Kelvin Yuen Kwong Chan A1 Mary Hoi Yin Tang A1 Christopher Chun Yu Mak A1 Gordon Ka Chun Leung A1 Po Lam So A1 Rolph Pfundt A1 Christian R Marshall A1 Stephen W Scherer A1 Sanaa Choufani A1 Rosanna Weksberg A1 Brian Hon-Yin Chung YR 2018 UL http://jmg.bmj.com/content/55/12/847.abstract AB Background We report here clinical, cytogenetic and molecular data for a pair of monochorionic diamniotic twins with paternal isodisomy for chromosome 19. Both twins presented with dysmorphic features and global developmental delay. This represents, to our knowledge, the first individual human case of paternal uniparental disomy for chromosome 19 (UPD19).Methods Whole-exome sequencing, together with conventional karyotype and SNP array analysis were performed along with genome-wide DNA methylation array for delineation of the underlying molecular defects.Results Conventional karyotyping on amniocytes and lymphocytes showed normal karyotypes for both twins. Whole-exome sequencing did not identify any pathogenic sequence variants but >5000 homozygous exonic variants on chromosome 19, suggestive of UPD19. SNP arrays on blood and buccal DNA both showed paternal isodisomy for chromosome 19. Losses of imprinting for known imprinted genes on chromosome 19 were identified, including ZNF331, PEG3, ZIM2 and MIMT1. In addition, imprinting defects were also identified in genes located on other chromosomes, including GPR1-AS, JAKMP1 and NHP2L1.Conclusion Imprinting defects are the most likely cause for the dysmorphism and developmental delay in this first report of monozygotic twins with UPD19. However, epigenotype-phenotype correlation will require identification of additional individuals with UPD19 and further molecular analysis.