单亲二体
遗传学
生物
基因组印记
外显子组测序
印记(心理学)
核型
SNP阵列
染色体
DNA甲基化
表型
单核苷酸多态性
基因
基因型
基因表达
作者
Kit San Yeung,Mandy Ho,So Lun Lee,Anita Sik Yau Kan,Kelvin Y.K. Chan,Mary Hoi Yin Tang,Christopher Chun Yu Mak,Gordon Leung,Po Lam So,Rolph Pfundt,Christian R. Marshall,Stephen W. Scherer,Sanaa Choufani,Rosanna Weksberg,Brian Hon‐Yin Chung
标识
DOI:10.1136/jmedgenet-2018-105328
摘要
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.
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