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Article Dans Une Revue Human Genetics Année : 2022

MYT1L-associated neurodevelopmental disorder: description of 40 new cases and literature review of clinical and molecular aspects

Juliette Coursimault (1) , Anne-Marie Guerrot (1) , Michelle Morrow (2) , Catherine Schramm (1) , Francisca Millan Zamora (2) , Anita Shanmugham (2) , Shuxi Liu (2) , Fanggeng Zou (2) , Frédéric Bilan (3) , Gwenaël Le Guyader (3) , Ange-Line Bruel (4) , Anne-Sophie Denommé-Pichon (4) , Laurence Faivre (4) , Frédéric Tran Mau-Them (4) , Marine Tessarech (5) , Estelle Colin (5) , Salima El Chehadeh (6) , Bénédicte Gérard (6) , Elise Schaefer (6) , Benjamin Cogne (7) , Bertrand Isidor (7) , Mathilde Nizon (7) , Diane Doummar (8, 9) , Stéphanie Valence (9) , Delphine Héron (9) , Boris Keren (9) , Cyril Mignot (9) , Charles Coutton (10) , Françoise Devillard (11) , Anne-Sophie Alaix (12) , Jeanne Amiel (12) , Laurence Colleaux (13, 14) , Arnold Munnich (12) , Karine Poirier (12) , Marlène Rio (12) , Sophie Rondeau (12) , Giulia Barcia (12) , Bert Callewaert (15) , Annelies Dheedene (15) , Candy Kumps (15) , Sarah Vergult (15) , Björn Menten (15) , Wendy Chung (16) , Rebecca Hernan (16) , Austin Larson (17) , Kelly Nori (17) , Sarah Stewart (17) , James Wheless (18) , Christina Kresge (19) , Beth Pletcher (19) , Roseline Caumes (20) , Thomas Smol (20) , Sabine Sigaudy (21) , Christine Coubes (22) , Margaret Helm (23) , Rosemarie Smith (23) , Jennifer Morrison (24) , Patricia Wheeler (24) , Amy Kritzer (25) , Guillaume Jouret (26) , Alexandra Afenjar (9) , Jean-François Deleuze (27) , Robert Olaso (27) , Anne Boland (27) , Christine Poitou (28) , Thierry Frebourg (1) , Claude Houdayer (1) , Pascale Saugier-Veber (1) , Gaël Nicolas (1) , François Lecoquierre (1)
Thomas Smol
  • Fonction : Auteur
Christine Coubes
  • Fonction : Auteur
Alexandra Afenjar
  • Fonction : Auteur
  • PersonId : 902592
François Lecoquierre

Résumé

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.
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Dates et versions

hal-03820933 , version 1 (03-02-2023)

Identifiants

Citer

Juliette Coursimault, Anne-Marie Guerrot, Michelle Morrow, Catherine Schramm, Francisca Millan Zamora, et al.. MYT1L-associated neurodevelopmental disorder: description of 40 new cases and literature review of clinical and molecular aspects. Human Genetics, 2022, 141 (1), pp.65-80. ⟨10.1007/s00439-021-02383-z⟩. ⟨hal-03820933⟩
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