Gain-of-function DNMT3A mutations cause microcephalic dwarfism and hypermethylation of Polycomb-regulated regions

• Published in: Nature genetics Vol. 51; no. 1; pp. 96 - 105
• Main Authors: Heyn, Patricia, Logan, Clare V., Fluteau, Adeline, Challis, Rachel C., Auchynnikava, Tatsiana, Martin, Carol-Anne, Marsh, Joseph A., Taglini, Francesca, Kilanowski, Fiona, Parry, David A., Cormier-Daire, Valerie, Fong, Chin-To, Gibson, Kate, Hwa, Vivian, Ibáñez, Lourdes, Robertson, Stephen P., Sebastiani, Giorgia, Rappsilber, Juri, Allshire, Robin C., Reijns, Martin A. M., Dauber, Andrew, Sproul, Duncan, Jackson, Andrew P.
• Format: Journal Article
• Language: English
• Published: New York Nature Publishing Group US 01.01.2019; Nature Publishing Group
• Subjects: 13; 13/1; 13/106; 38; 38/23; 38/91; 631/208; 631/208/176; 64; 64/60; 82; 82/58; 82/79; Agriculture; Amino acids; Animal Genetics and Genomics; Animals; Bioinformatics; Biomedical and Life Sciences; Biomedicine; Cancer Research; Cell cycle; Cell Line, Tumor; Cells, Cultured; Deoxyribonucleic acid; Depletion; DNA; DNA (Cytosine-5-)-Methyltransferases - genetics; DNA methylation; DNA Methylation - genetics; DNA methyltransferase; DNA Methyltransferase 3A; DNA Modification Methylases - genetics; Domains; Dwarfism; Dwarfism - genetics; Female; Fibroblasts; Gain of Function Mutation - genetics; Gene expression; Gene Function; Gene mutation; Genomes; HeLa Cells; Histones - genetics; Human Genetics; Humans; Male; Methylation; Methyltransferases; Mice; Mice, Transgenic - genetics; Microcephaly; Microcephaly - genetics; Missense mutation; Mutation; Patients; Peptides; Pluripotency; Polycomb group proteins; Polycomb-Group Proteins - genetics; Protein Binding - genetics; Proteins; Regulators; Regulatory Sequences, Nucleic Acid - genetics; Stem cells; Transferases

DNA methylation and Polycomb are key factors in the establishment of vertebrate cellular identity and fate. Here we report de novo missense mutations in DNMT3A , which encodes the DNA methyltransferase DNMT3A. These mutations cause microcephalic dwarfism, a hypocellular disorder of extreme global gr...