BRAT1-related disorders: phenotypic spectrum and phenotype-genotype correlations from 97 patients.
Journal
European journal of human genetics : EJHG
ISSN: 1476-5438
Titre abrégé: Eur J Hum Genet
Pays: England
ID NLM: 9302235
Informations de publication
Date de publication:
09 2023
09 2023
Historique:
received:
22
12
2022
accepted:
07
06
2023
revised:
26
04
2023
pmc-release:
01
09
2024
medline:
4
9
2023
pubmed:
22
6
2023
entrez:
21
6
2023
Statut:
ppublish
Résumé
BRAT1 biallelic variants are associated with rigidity and multifocal seizure syndrome, lethal neonatal (RMFSL), and neurodevelopmental disorder associating cerebellar atrophy with or without seizures syndrome (NEDCAS). To date, forty individuals have been reported in the literature. We collected clinical and molecular data from 57 additional cases allowing us to study a large cohort of 97 individuals and draw phenotype-genotype correlations. Fifty-nine individuals presented with BRAT1-related RMFSL phenotype. Most of them had no psychomotor acquisition (100%), epilepsy (100%), microcephaly (91%), limb rigidity (93%), and died prematurely (93%). Thirty-eight individuals presented a non-lethal phenotype of BRAT1-related NEDCAS phenotype. Seventy-six percent of the patients in this group were able to walk and 68% were able to say at least a few words. Most of them had cerebellar ataxia (82%), axial hypotonia (79%) and cerebellar atrophy (100%). Genotype-phenotype correlations in our cohort revealed that biallelic nonsense, frameshift or inframe deletion/insertion variants result in the severe BRAT1-related RMFSL phenotype (46/46; 100%). In contrast, genotypes with at least one missense were more likely associated with NEDCAS (28/34; 82%). The phenotype of patients carrying splice variants was variable: 41% presented with RMFSL (7/17) and 59% with NEDCAS (10/17).
Identifiants
pubmed: 37344571
doi: 10.1038/s41431-023-01410-z
pii: 10.1038/s41431-023-01410-z
pmc: PMC10474045
doi:
Substances chimiques
Nuclear Proteins
0
BRAT1 protein, human
0
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Research Support, N.I.H., Extramural
Langues
eng
Sous-ensembles de citation
IM
Pagination
1023-1031Subventions
Organisme : NINDS NIH HHS
ID : K23 NS119666
Pays : United States
Organisme : NICHD NIH HHS
ID : P50 HD105351
Pays : United States
Informations de copyright
© 2023. The Author(s), under exclusive licence to European Society of Human Genetics.
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