| Literature DB >> 34748075 |
Juliette Coursimault1, Anne-Marie Guerrot1, Michelle M Morrow2, Catherine Schramm1, Francisca Millan Zamora2, Anita Shanmugham2, Shuxi Liu2, Fanggeng Zou2, Frédéric Bilan3, Gwenaël Le Guyader3, Ange-Line Bruel4,5, Anne-Sophie Denommé-Pichon4,5, Laurence Faivre4,6, Frédéric Tran Mau-Them4,5, Marine Tessarech7, Estelle Colin7,8, Salima El Chehadeh9, Bénédicte Gérard9, Elise Schaefer9, Benjamin Cogne10, Bertrand Isidor10, Mathilde Nizon10, Diane Doummar11, Stéphanie Valence11, Delphine Héron12, Boris Keren12, Cyril Mignot12, Charles Coutton13, Françoise Devillard14, Anne-Sophie Alaix15, Jeanne Amiel15, Laurence Colleaux15, Arnold Munnich15, Karine Poirier15, Marlène Rio15, Sophie Rondeau15, Giulia Barcia15, Bert Callewaert16, Annelies Dheedene16, Candy Kumps16, Sarah Vergult16, Björn Menten16, Wendy K Chung17, Rebecca Hernan17, Austin Larson18, Kelly Nori18, Sarah Stewart18, James Wheless19, Christina Kresge20, Beth A Pletcher20, Roseline Caumes21, Thomas Smol22, Sabine Sigaudy23, Christine Coubes24, Margaret Helm25, Rosemarie Smith25, Jennifer Morrison26, Patricia G Wheeler26, Amy Kritzer27, Guillaume Jouret28, Alexandra Afenjar29, Jean-François Deleuze30, Robert Olaso30, Anne Boland30, Christine Poitou31, Thierry Frebourg1, Claude Houdayer1, Pascale Saugier-Veber1, Gaël Nicolas1, François Lecoquierre32.
Abstract
Pathogenic variants of the myelin transcription factor-1 like (MYT1L) gene include heterozygous missense, truncating variants and 2p25.3 microdeletions and cause a syndromic neurodevelopmental disorder (OMIM#616,521). Despite enrichment in de novo mutations in several developmental disorders and autism studies, the data on clinical characteristics and genotype-phenotype correlations are scarce, with only 22 patients with single nucleotide pathogenic variants reported. We aimed to further characterize this disorder at both the clinical and molecular levels by gathering a large series of patients with MYT1L-associated neurodevelopmental disorder. We collected genetic information on 40 unreported patients with likely pathogenic/pathogenic MYT1L variants and performed a comprehensive review of published data (total = 62 patients). We confirm that the main phenotypic features of the MYT1L-related disorder are developmental delay with language delay (95%), intellectual disability (ID, 70%), overweight or obesity (58%), behavioral disorders (98%) and epilepsy (23%). We highlight novel clinical characteristics, such as learning disabilities without ID (30%) and feeding difficulties during infancy (18%). We further describe the varied dysmorphic features (67%) and present the changes in weight over time of 27 patients. We show that patients harboring highly clustered missense variants in the 2-3-ZNF domains are not clinically distinguishable from patients with truncating variants. We provide an updated overview of clinical and genetic data of the MYT1L-associated neurodevelopmental disorder, hence improving diagnosis and clinical management of these patients.Entities:
Mesh：
Substances：
Year: 2021 PMID： 34748075 DOI： 10.1007/s00439-021-02383-z
Source DB: PubMed Journal: Hum Genet ISSN： 0340-6717 Impact factor: 4.132