Fetal anomalies
Gene: RAC1

RAC1 (Rac family small GTPase 1)
EnsemblGeneIds (GRCh38): ENSG00000136238
EnsemblGeneIds (GRCh37): ENSG00000136238
OMIM: 602048, Gene2Phenotype
RAC1 is in 6 panels

1 review

Zornitza Stark (Victorian Clinical Genetics Services; Australian Genomics)

Green List (high evidence)

At least 7 individuals reported so far, all variants missense, most de novo. Hotspot/cluster in GTP binding motif.1 paper postulated toxic GoF as the mechanism of disease (PMID: 30293988), however another suggested LoF, and functional studies have yet to be performed in patient cells (PMID: 30042656). Phenotypic variability may be related to mutational mechanism.
The phenotype was highly variable: 1 patient had an IQ of 35 at age 13, several had poor or absent speech, and several had delayed or impaired walking. Other neurologic features included poor feeding, hypotonia (in 4 patients), seizures (3), behavioral problems (3), and stereotypical movements (3). Four patients had microcephaly (-2.5 to -5 SD), 1 was normocephalic, and 2 had macrocephaly (+4.16 and +4.5 SD). Most patients had dysmorphic facial features, although there was not a common recognizable gestalt. Features included arched eyebrows, dysplastic ears, prominent nasal bridge, upturned nose, overhanging columella, long palpebral fissures, and broad or open mouth. One patient had sensorineural hearing loss and mild visual impairment. Brain imaging was abnormal in all 6 patients who were studied, although these findings were also highly variable. Common abnormalities included cerebellar hypoplasia, cerebellar dysplasia, hypoplasia of the corpus callosum, enlarged ventricles, mega cisterna magna, and thin brainstem. One patient had polymicrogyria. The 2 patients with macrocephaly had only nonspecific periventricular white matter lesions. Other less common extraneurologic features included hypospadias, cardiac abnormalities, recurrent infections, and eczema.
Created: 6 Aug 2020, 7:53 a.m. | Last Modified: 6 Aug 2020, 7:53 a.m.

Panel Version: 0.2823

Mode of inheritance
MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted

Phenotypes
Mental retardation, autosomal dominant 48 617751

Publications

Mode of pathogenicity
Other

Created: 6 Aug 2020, 7:53 a.m.
Last Modified: 6 Aug 2020, 7:53 a.m.
Panel version: Imported from Intellectual disability syndromic and non-syndromic panel version 0.2823

Details

Mode of Inheritance

MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted

Sources

Expert Review Green
Genomics England PanelApp
Genetic Health Queensland

Phenotypes

Mental retardation, autosomal dominant 48, MIM# 617751

OMIM

602048

Clinvar variants

Variants in RAC1

Penetrance

None

Publications

Mode of Pathogenicity

Other

Panels with this gene