Nine newly identified individuals refine the phenotype associated with MYT1L mutations.
Adolescent
Adult
Child
Child, Preschool
Chromosome Deletion
Chromosomes, Human, Pair 2
/ genetics
Female
Genetic Predisposition to Disease
Haploinsufficiency
/ genetics
Humans
Intellectual Disability
/ genetics
Male
Microarray Analysis
Microcephaly
/ genetics
Nerve Tissue Proteins
/ genetics
Obesity
/ genetics
Phenotype
Point Mutation
Polymorphism, Single Nucleotide
/ genetics
Transcription Factors
/ genetics
Exome Sequencing
Young Adult
MYT1L
chromosomal microarray
intellectual disability
microdeletion 2p25.3
obesity
whole exome sequencing
Journal
American journal of medical genetics. Part A
ISSN: 1552-4833
Titre abrégé: Am J Med Genet A
Pays: United States
ID NLM: 101235741
Informations de publication
Date de publication:
05 2020
05 2020
Historique:
received:
07
11
2019
revised:
16
01
2020
accepted:
28
01
2020
pubmed:
18
2
2020
medline:
13
1
2021
entrez:
18
2
2020
Statut:
ppublish
Résumé
Both point mutations and deletions of the MYT1L gene as well as microdeletions of chromosome band 2p25.3 including MYT1L are associated with intellectual disability, obesity, and behavioral problems. Thus, MYT1L is assumed to be the-at least mainly-causative gene in the 2p25.3 deletion syndrome. Here, we present comprehensive descriptions of nine novel individuals bearing MYT1L mutations; most of them single nucleotide variants (SNVs). This increases the number of known individuals with causative deletions or SNVs of MYT1L to 51. Since eight of the nine novel patients bear mutations affecting MYT1L only, the total number of such individuals now nearly equals the number of individuals with larger microdeletions affecting additional genes, allowing for a comprehensive phenotypic comparison of these two patient groups. For example, 55% of the individuals with mutations affecting MYT1L only were overweight or obese as compared to 86% of the individuals with larger microdeletions. A similar trend was observed regarding short stature with 5 versus 35%, respectively. However, these differences were nominally significant only after correction for multiple testing, further supporting the hypothesis that MYT1L haploinsufficiency is central to the 2p25.3 deletion phenotype. Most importantly, the large number of individuals with MYT1L mutations presented and reviewed here allowed for the delineation of a more comprehensive clinical picture. Seizures, postnatal short stature, macrocephaly, and microcephaly could be shown to be over-represented among individuals with MYT1L mutations.
Identifiants
pubmed: 32065501
doi: 10.1002/ajmg.a.61515
doi:
Substances chimiques
MYT1L protein, human
0
Nerve Tissue Proteins
0
Transcription Factors
0
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
1021-1031Informations de copyright
© 2020 The Authors. American Journal of Medical Genetics Part A published by Wiley Periodicals, Inc.
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