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)
1
UNIROUEN -
Université de Rouen Normandie
2 GeneDx [Gaithersburg, MD, USA]
3 CHU de Poitiers [La Milétrie] - Centre hospitalier universitaire de Poitiers = Poitiers University Hospital
4 UBFC - Université Bourgogne Franche-Comté [COMUE]
5 CHU Angers - Centre Hospitalier Universitaire d'Angers
6 IGMA - Institut de génétique médicale d’Alsace
7 CHU Nantes - Centre Hospitalier Universitaire de Nantes = Nantes University Hospital
8 Hôpital Trousseau
9 SU - Sorbonne Université
10 IAB - Institute for Advanced Biosciences / Institut pour l'Avancée des Biosciences (Grenoble)
11 CHUGA - Centre Hospitalier Universitaire [CHU Grenoble]
12 INEM - UM 111 (UMR 8253 / U1151) - Institut Necker Enfants-Malades
13 MMG - Marseille medical genetics - Centre de génétique médicale de Marseille
14 IMAGINE - U1163 - Imagine - Institut des maladies génétiques
15 Ghent University Hospital
16 CUIMC - Columbia University Irving Medical Center
17 University of Colorado Anschutz [Aurora]
18 University of Tennessee System
19 NJMS - Rutgers New Jersey Medical School
20 Université de Lille
21 TIMONE - Hôpital de la Timone [CHU - APHM]
22 CHU Montpellier
23 Maine Medical Center
24 Arnold Palmer Hospital
25 Boston Children's Hospital
26 National Center of Genetics
27 CNRGH - Centre National de Recherche en Génomique Humaine
28 CHU Pitié-Salpêtrière [AP-HP]
2 GeneDx [Gaithersburg, MD, USA]
3 CHU de Poitiers [La Milétrie] - Centre hospitalier universitaire de Poitiers = Poitiers University Hospital
4 UBFC - Université Bourgogne Franche-Comté [COMUE]
5 CHU Angers - Centre Hospitalier Universitaire d'Angers
6 IGMA - Institut de génétique médicale d’Alsace
7 CHU Nantes - Centre Hospitalier Universitaire de Nantes = Nantes University Hospital
8 Hôpital Trousseau
9 SU - Sorbonne Université
10 IAB - Institute for Advanced Biosciences / Institut pour l'Avancée des Biosciences (Grenoble)
11 CHUGA - Centre Hospitalier Universitaire [CHU Grenoble]
12 INEM - UM 111 (UMR 8253 / U1151) - Institut Necker Enfants-Malades
13 MMG - Marseille medical genetics - Centre de génétique médicale de Marseille
14 IMAGINE - U1163 - Imagine - Institut des maladies génétiques
15 Ghent University Hospital
16 CUIMC - Columbia University Irving Medical Center
17 University of Colorado Anschutz [Aurora]
18 University of Tennessee System
19 NJMS - Rutgers New Jersey Medical School
20 Université de Lille
21 TIMONE - Hôpital de la Timone [CHU - APHM]
22 CHU Montpellier
23 Maine Medical Center
24 Arnold Palmer Hospital
25 Boston Children's Hospital
26 National Center of Genetics
27 CNRGH - Centre National de Recherche en Génomique Humaine
28 CHU Pitié-Salpêtrière [AP-HP]
Laurence Colleaux
- Fonction : Auteur
- PersonId : 184021
- IdHAL : laurence-colleaux
- ORCID : 0000-0002-0987-7648
- IdRef : 033661782
Thierry Frebourg
- Fonction : Auteur
- PersonId : 757398
- ORCID : 0000-0003-0399-4007
- IdRef : 074620916
François Lecoquierre
- Fonction : Auteur
- PersonId : 793170
- ORCID : 0000-0002-9110-1856
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.
Domaines
Génétique humaine| Origine | Fichiers produits par l'(les) auteur(s) |
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