De novo CLCN3 variants affecting Gly327 cause severe neurodevelopmental syndrome with brain structural abnormalities.
Journal
Journal of human genetics
ISSN: 1435-232X
Titre abrégé: J Hum Genet
Pays: England
ID NLM: 9808008
Informations de publication
Date de publication:
Apr 2023
Apr 2023
Historique:
received:
22
07
2022
accepted:
05
12
2022
revised:
26
10
2022
medline:
28
3
2023
pubmed:
20
12
2022
entrez:
19
12
2022
Statut:
ppublish
Résumé
A recent study revealed that monoallelic missense or biallelic loss-of-function variants in the chloride voltage-gated channel 3 (CLCN3) cause neurodevelopmental disorders resulting in brain abnormalities. Functional studies suggested that some missense variants had varying gain-of-function effects on channel activity. Meanwhile, two patients with homozygous frameshift variants showed severe neuropsychiatric disorders and a range of brain structural abnormalities. Here we describe two patients with de novo CLCN3 variants affecting the same amino acid, Gly327 (p.(Gly327Ser) and p.(Gly327Asp)). They showed severe neurological phenotypes including global developmental delay, intellectual disability, hypotonia, failure to thrive, and various brain abnormalities. They also presented with characteristic brain and ophthalmological abnormalities, hippocampal and retinal degradation, which were observed in patients harboring homozygous loss-of-function variants. These findings were also observed in CLCN3-deficient mice, indicating that the monoallelic missense variant may also have a dominant negative effect. This study will expand the phenotypic spectrum of CLCN3-related disorders.
Identifiants
pubmed: 36536096
doi: 10.1038/s10038-022-01106-0
pii: 10.1038/s10038-022-01106-0
doi:
Substances chimiques
ClC-3 channel
0
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
291-298Informations de copyright
© 2022. The Author(s), under exclusive licence to The Japan Society of Human Genetics.
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