The phenotypic and genotypic spectrum of individuals with mono- or biallelic ANK3 variants.
aggressivity
ankyrin‐G
autism spectrum disorder
epilepsy
hypotonia
intellectual disability
language delay
neurodevelopmental disorder
sleep disturbances
Journal
Clinical genetics
ISSN: 1399-0004
Titre abrégé: Clin Genet
Pays: Denmark
ID NLM: 0253664
Informations de publication
Date de publication:
11 Jul 2024
11 Jul 2024
Historique:
revised:
25
06
2024
received:
03
05
2024
accepted:
28
06
2024
medline:
11
7
2024
pubmed:
11
7
2024
entrez:
11
7
2024
Statut:
aheadofprint
Résumé
ANK3 encodes ankyrin-G, a protein involved in neuronal development and signaling. Alternative splicing gives rise to three ankyrin-G isoforms comprising different domains with distinct expression patterns. Mono- or biallelic ANK3 variants are associated with non-specific syndromic intellectual disability in 14 individuals (seven with monoallelic and seven with biallelic variants). In this study, we describe the clinical features of 13 additional individuals and review the data on a total of 27 individuals (16 individuals with monoallelic and 11 with biallelic ANK3 variants) and demonstrate that the phenotype for biallelic variants is more severe. The phenotypic features include language delay (92%), autism spectrum disorder (76%), intellectual disability (78%), hypotonia (65%), motor delay (68%), attention deficit disorder (ADD) or attention deficit hyperactivity disorder (ADHD) (57%), sleep disturbances (50%), aggressivity/self-injury (37.5%), and epilepsy (35%). A notable phenotypic difference was presence of ataxia in three individuals with biallelic variants, but in none of the individuals with monoallelic variants. While the majority of the monoallelic variants are predicted to result in a truncated protein, biallelic variants are almost exclusively missense. Moreover, mono- and biallelic variants appear to be localized differently across the three different ankyrin-G isoforms, suggesting isoform-specific pathological mechanisms.
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Subventions
Organisme : NHGRI NIH HHS
ID : U01 HG011744
Pays : United States
Organisme : NHGRI NIH HHS
ID : U24 HG011746
Pays : United States
Organisme : Netherlands Organisation for Scientific Research
ID : 09150172110002
Organisme : Italian Ministry of Health
Organisme : Italian Ministry of University and Research
ID : PRIN2022
Organisme : Italian Ministry of University and Research
ID : PRIN PNRR 2022
Organisme : P50HD109879
Organisme : Spanish Government
ID : RTI2018-094434-B-I00
Organisme : Spanish Government
ID : PID2021-126625OB-I00
Informations de copyright
© 2024 The Author(s). Clinical Genetics published by John Wiley & Sons Ltd.
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