Cross-sectional quantitative analysis of the natural history of TUBA1A and TUBB2B tubulinopathies.
TUBA1A
TUBB2B
malformations of cortical development
natural history
tubulinopathy
Journal
Genetics in medicine : official journal of the American College of Medical Genetics
ISSN: 1530-0366
Titre abrégé: Genet Med
Pays: United States
ID NLM: 9815831
Informations de publication
Date de publication:
03 2021
03 2021
Historique:
received:
21
07
2020
accepted:
28
09
2020
revised:
25
09
2020
pubmed:
22
10
2020
medline:
4
6
2021
entrez:
21
10
2020
Statut:
ppublish
Résumé
TUBA1A and TUBB2B tubulinopathies are rare neurodevelopmental disorders characterized by cortical and extracortical malformations and heterogenic phenotypes. There is a need for quantitative clinical endpoints that will be beneficial for future diagnostic and therapeutic trials. Quantitative natural history modeling of individuals with TUBA1A and TUBB2B tubulinopathies from clinical reports and database entries of DECIPHER and ClinVar. Main outcome measures were age at disease onset, survival, and diagnostic delay. Phenotypical, neuroradiological, and histopathological features were descriptively illustrated. Mean age at disease onset was 4 (TUBA1A) and 6 months (TUBB2B), respectively. Mortality was equally estimated with 7% at 3.2 (TUBA1A) and 8.0 years (TUBB2B). Diagnostic delay was significantly higher in TUBB2B (12.3 years) compared with TUBA1A tubulinopathy (4.2 years). We delineated the isotype-dependent clinical, neuroradiological, and histopathological phenotype of affected individuals and present brain malformations associated with epilepsy and an unfavorable course of disease. The natural history of tubulinopathies is defined by the genotype and associated brain malformations. Defined data on estimated survival, diagnostic delay, and disease characteristics of TUBA1A and TUBB2B tubulinopathy will help to raise disease awareness and encourage future clinical trials to optimize genetic testing, family counseling, and supportive care.
Identifiants
pubmed: 33082561
doi: 10.1038/s41436-020-01001-z
pii: S1098-3600(21)04941-8
pmc: PMC7935713
doi:
Substances chimiques
TUBA1A protein, human
0
TUBB2B protein, human
0
Tubulin
0
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
516-523Subventions
Organisme : Wellcome Trust
Pays : United Kingdom
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