Cerebral vascular malformations

Gene: ARX

Red List (low evidence)

ARX (aristaless related homeobox)
EnsemblGeneIds (GRCh38): ENSG00000004848
EnsemblGeneIds (GRCh37): ENSG00000004848
OMIM: 300382, Gene2Phenotype
ARX is in 20 panels

2 reviews

Sangavi Sivagnanasundram (Melbourne Health)

Red List (low evidence)

not associated with cerebral vascular malformations
Created: 25 Nov 2024, 10:45 p.m. | Last Modified: 25 Nov 2024, 10:45 p.m.
Panel Version: 0.39

Elena Savva (Victorian Clinical Genetics Services)

Green List (high evidence)

Poly-Ala expansion – EE and ID phenotypes, no brain abnormalilties (PMID: 21496008, OMIM)
NMD PTCs – Brain abnormailities including hydranencephaly, lissencephaly, Proud syndrome (PMID: 14722918, OMIM).
NMD PTCs in the first ~40aa – West/Otahara syndrome, avoid brain abnormalities due to re-initiation of translation at p.Met41 (PMID: 19738637).
Missense - all phenotypes but less severe, severity depends on variant location and protein conservation at that position (PMID: 14722918).

Affected females with PTCs show agenesis of the corpus callosum. Variable expressivity, some are unaffected - no X skewing found in affected females (PMID: 14722918, PMID: 28150386, PMID: 32519823).

Missense and polyA expansions cause protein mislocalization. More poly-Ala expansion = more mislocalization = more severe phenotype (PMID: 14722918). Loss of DNA binding ability is also reported (OMIM).

Variable pleiotrophy well reported within families. Same mutations are reported with different phenotypes (OMIM).
Created: 9 Oct 2020, 3:01 a.m. | Last Modified: 9 Oct 2020, 3:01 a.m.
Panel Version: 0.4843

Mode of inheritance
X-LINKED: hemizygous mutation in males, monoallelic mutations in females may cause disease (may be less severe, later onset than males)

Phenotypes
Epileptic encephalopathy, early infantile, 1 MIM#308350; Hydranencephaly with abnormal genitalia MIM#300215; Lissencephaly, X-linked 2 MIM#300215; Mental retardation, X-linked 29 and others MIM#300419; Partington syndrome MIM#309510; Proud syndrome MIM#300004

Publications

Variants in this GENE are reported as part of current diagnostic practice

History Filter Activity

26 Nov 2024, Gel status: 1

Entity classified by Genomics England curator

Zornitza Stark (Victorian Clinical Genetics Services; Australian Genomics)

Gene: arx has been classified as Red List (Low Evidence).

18 May 2020, Gel status: 1

Created, Added New Source, Set mode of inheritance, Set Phenotypes

Zornitza Stark (Victorian Clinical Genetics Services; Australian Genomics)

gene: ARX was added gene: ARX was added to Cerebral vascular malformations. Sources: Expert Review Red,Genomics England PanelApp Mode of inheritance for gene: ARX was set to Phenotypes for gene: ARX were set to Cerebral Malformation Disorders