TY - JOUR 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 SP - 847 LP - 852 DO - 10.1136/jmedgenet-2018-105328 VL - 55 IS - 12 AU - Kit San Yeung AU - Matthew Sai Pong Ho AU - So Lun Lee AU - Anita Sik Yau Kan AU - Kelvin Yuen Kwong Chan AU - Mary Hoi Yin Tang AU - Christopher Chun Yu Mak AU - Gordon Ka Chun Leung AU - Po Lam So AU - Rolph Pfundt AU - Christian R Marshall AU - Stephen W Scherer AU - Sanaa Choufani AU - Rosanna Weksberg AU - Brian Hon-Yin Chung Y1 - 2018/12/01 UR - http://jmg.bmj.com/content/55/12/847.abstract N2 - 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. ER -