O'Donnell-Luria-Rodan syndrome: description of a second multinational cohort and refinement of the phenotypic spectrum.

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Etat: Public
Version: de l'auteur⸱e
Licence: Non spécifiée
ID Serval
serval:BIB_83FFDC95F451
Type
Article: article d'un périodique ou d'un magazine.
Collection
Publications
Institution
Titre
O'Donnell-Luria-Rodan syndrome: description of a second multinational cohort and refinement of the phenotypic spectrum.
Périodique
Journal of medical genetics
Auteur⸱e⸱s
Velmans C., O'Donnell-Luria A.H., Argilli E., Tran Mau-Them F., Vitobello A., Chan M.C., Fung J.L., Rech M., Abicht A., Aubert Mucca M., Carmichael J., Chassaing N., Clark R., Coubes C., Denommé-Pichon A.S., de Dios J.K., England E., Funalot B., Gerard M., Joseph M., Kennedy C., Kumps C., Willems M., van de Laar IMBH, Aarts-Tesselaar C., van Slegtenhorst M., Lehalle D., Leppig K., Lessmeier L., Pais L.S., Paterson H., Ramanathan S., Rodan L.H., Superti-Furga A., Chung BHY, Sherr E., Netzer C., Schaaf C.P., Erger F.
ISSN
1468-6244 (Electronic)
ISSN-L
0022-2593
Statut éditorial
Publié
Date de publication
07/2022
Peer-reviewed
Oui
Volume
59
Numéro
7
Pages
697-705
Langue
anglais
Notes
Publication types: Journal Article
Publication Status: ppublish
Résumé
O'Donnell-Luria-Rodan syndrome (ODLURO) is an autosomal-dominant neurodevelopmental disorder caused by pathogenic, mostly truncating variants in KMT2E. It was first described by O'Donnell-Luria et al in 2019 in a cohort of 38 patients. Clinical features encompass macrocephaly, mild intellectual disability (ID), autism spectrum disorder (ASD) susceptibility and seizure susceptibility.
Affected individuals were ascertained at paediatric and genetic centres in various countries by diagnostic chromosome microarray or exome/genome sequencing. Patients were collected into a case cohort and were systematically phenotyped where possible.
We report 18 additional patients from 17 families with genetically confirmed ODLURO. We identified 15 different heterozygous likely pathogenic or pathogenic sequence variants (14 novel) and two partial microdeletions of KMT2E. We confirm and refine the phenotypic spectrum of the KMT2E-related neurodevelopmental disorder, especially concerning cognitive development, with rather mild ID and macrocephaly with subtle facial features in most patients. We observe a high prevalence of ASD in our cohort (41%), while seizures are present in only two patients. We extend the phenotypic spectrum by sleep disturbances.
Our study, bringing the total of known patients with ODLURO to more than 60 within 2 years of the first publication, suggests an unexpectedly high relative frequency of this syndrome worldwide. It seems likely that ODLURO, although just recently described, is among the more common single-gene aetiologies of neurodevelopmental delay and ASD. We present the second systematic case series of patients with ODLURO, further refining the mutational and phenotypic spectrum of this not-so-rare syndrome.
Mots-clé
Autism Spectrum Disorder/genetics, Child, Humans, Intellectual Disability/diagnosis, Intellectual Disability/epidemiology, Intellectual Disability/genetics, Megalencephaly, Neurodevelopmental Disorders, Seizures/epidemiology, Seizures/genetics, Syndrome, Whole Exome Sequencing, behavioural, genetic counselling, genetics, human genetics, mutation
Pubmed
Web of science
Création de la notice
06/08/2021 11:32
Dernière modification de la notice
06/07/2022 5:35
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