Biallelic CACNA1A variants: Review of literature and report of a child with drug-resistant epilepsy and developmental delay.
CACNA1A
biallelic
cerebellar atrophy
epileptic encephalopathy
intellectual disability
recessive
Journal
American journal of medical genetics. Part A
ISSN: 1552-4833
Titre abrégé: Am J Med Genet A
Pays: United States
ID NLM: 101235741
Informations de publication
Date de publication:
11 2022
11 2022
Historique:
revised:
19
07
2022
received:
31
03
2022
accepted:
24
07
2022
pubmed:
6
9
2022
medline:
12
10
2022
entrez:
5
9
2022
Statut:
ppublish
Résumé
Biallelic variants in CACNA1A have previously been reported in nine individuals (four families) presenting with epilepsy and cognitive impairments of variable severity and age-of-onset. Here, we describe a child who presented at 6 months of age with drug-resistant epilepsy and developmental delay. At 10 years of age, she has profound impairments in motor function and communication. MRI was initially unremarkable, but progressed to severe cerebellar atrophy by age 3 years. Next Generation Sequencing and panel analysis identified a maternally inherited truncating variant c.2042_2043delAG, p.(Gln681ArgfsTer100) and paternally inherited missense variant c.1693G>A, p.(Glu565Lys). In contrast to previously reported biallelic cases, parents carrying these monoallelic variants did not display clear signs of a CACNA1A-associated syndrome. In conclusion, we provide further evidence that biallelic CACNA1A variants can cause a severe epileptic and developmental encephalopathy with progressive cerebellar atrophy, and highlight complexities of genetic counseling in such situations.
Identifiants
pubmed: 36063114
doi: 10.1002/ajmg.a.62960
pmc: PMC9826308
doi:
Substances chimiques
CACNA1A protein, human
0
Calcium Channels
0
Types de publication
Case Reports
Review
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
3306-3311Subventions
Organisme : Medical Research Council
ID : MC_UU_00030/3
Pays : United Kingdom
Organisme : Medical Research Council
ID : G101400
Pays : United Kingdom
Organisme : Department of Health
ID : BRC-1215-20014
Pays : United Kingdom
Informations de copyright
© 2022 The Authors. American Journal of Medical Genetics Part A published by Wiley Periodicals LLC.
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