The neurodevelopmental and facial phenotype in individuals with a TRIP12 variant.
Details
Serval ID
serval:BIB_9F1FCE7610D3
Type
Article: article from journal or magazin.
Collection
Publications
Institution
Title
The neurodevelopmental and facial phenotype in individuals with a TRIP12 variant.
Journal
European journal of human genetics
ISSN
1476-5438 (Electronic)
ISSN-L
1018-4813
Publication state
Published
Issued date
04/2023
Peer-reviewed
Oui
Volume
31
Number
4
Pages
461-468
Language
english
Notes
Publication types: Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
Publication Status: ppublish
Publication Status: ppublish
Abstract
Haploinsufficiency of TRIP12 causes a neurodevelopmental disorder characterized by intellectual disability associated with epilepsy, autism spectrum disorder and dysmorphic features, also named Clark-Baraitser syndrome. Only a limited number of cases have been reported to date. We aimed to further delineate the TRIP12-associated phenotype and objectify characteristic facial traits through GestaltMatcher image analysis based on deep-learning algorithms in order to establish a TRIP12 gestalt. 38 individuals between 3 and 66 years (F = 20, M = 18) - 1 previously published and 37 novel individuals - were recruited through an ERN ITHACA call for collaboration. 35 TRIP12 variants were identified, including frameshift (n = 15) and nonsense (n = 6) variants, as well as missense (n = 5) and splice (n = 3) variants, intragenic deletions (n = 4) and two multigene deletions disrupting TRIP12. Though variable in severity, global developmental delay was noted in all individuals, with language deficit most pronounced. About half showed autistic features and susceptibility to obesity seemed inherent to this disorder. A more severe expression was noted in individuals with a missense variant. Facial analysis showed a clear gestalt including deep-set eyes with narrow palpebral fissures and fullness of the upper eyelids, downturned corners of the mouth and large, often low-set ears with prominent earlobes. We report the largest cohort to date of individuals with TRIP12 variants, further delineating the associated phenotype and introducing a facial gestalt. These findings will improve future counseling and patient guidance.
Keywords
Humans, Autism Spectrum Disorder/genetics, Intellectual Disability/genetics, Phenotype, Neurodevelopmental Disorders/genetics, Mutation, Missense, Carrier Proteins/genetics, Ubiquitin-Protein Ligases/genetics
Pubmed
Web of science
Create date
03/03/2023 10:05
Last modification date
28/10/2023 6:11