The phenotypic spectrum of ARHGEF9 includes intellectual disability, focal epilepsy and febrile seizures.
J Neurol
; 264(7): 1421-1425, 2017 Jul.
Article
in En
| MEDLINE
| ID: mdl-28620718
ABSTRACT
Mutations or structural genomic alterations of the X-chromosomal gene ARHGEF9 have been described in male and female patients with intellectual disability. Hyperekplexia and epilepsy were observed to a variable degree, but incompletely described. Here, we expand the phenotypic spectrum of ARHGEF9 by describing a large Ethiopian-Jewish family with epilepsy and intellectual disability. The four affected male siblings, their unaffected parents and two unaffected female siblings were recruited and phenotyped. Parametric linkage analysis was performed using SNP microarrays. Variants from exome sequencing in two affected individuals were confirmed by Sanger sequencing. All affected male siblings had febrile seizures from age 2-3 years and intellectual disability. Three developed afebrile seizures between age 7-17 years. Three showed focal seizure semiology. None had hyperekplexia. A novel ARHGEF9 variant (c.967G>A, p.G323R, NM_015185.2) was hemizygous in all affected male siblings and heterozygous in the mother. This family reveals that the phenotypic spectrum of ARHGEF9 is broader than commonly assumed and includes febrile seizures and focal epilepsy with intellectual disability in the absence of hyperekplexia or other clinically distinguishing features. Our findings suggest that pathogenic variants in ARHGEF9 may be more common than previously assumed in patients with intellectual disability and mild epilepsy.
Key words
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Epilepsies, Partial
/
Seizures, Febrile
/
Rho Guanine Nucleotide Exchange Factors
/
Intellectual Disability
Limits:
Adolescent
/
Adult
/
Female
/
Humans
/
Male
Language:
En
Journal:
J Neurol
Year:
2017
Document type:
Article