Severe microcephaly

Gene: ADARB1

The rating of this gene has been updated following NHS Genomic Medicine Service approval.

Created: 10 Mar 2022, 10:52 a.m. | Last Modified: 10 Mar 2022, 10:52 a.m.

Panel Version: 2.282

Comment on list classification: There is enough evidence for this gene to be rated GREEN at the next major review.

Created: 9 Jul 2020, 1:21 p.m. | Last Modified: 9 Jul 2020, 1:21 p.m.

Panel Version: 2.11

Green List (high evidence)

PMID: 32719099 (2020) - Three additional patients from two consanguineous families with novel biallelic variants in the ADARB1 gene. All affected individuals presented global DD, severe-profound ID, intractable early infantile-onset seizures, severe microcephaly, axial hypotonia and progressive appendicular spasticity. In vitro RNA editing assays showed that both variants resulted in severe impairment or loss of ADAR2 enzymatic activity.

Created: 1 Sep 2020, 12:47 p.m. | Last Modified: 1 Sep 2020, 12:47 p.m.

Panel Version: 2.19

Gene is associated with phenotype in OMIM and G2P.

PMID: 32220291 - Bi-allelic variants reported in four unrelated individuals with severe/profound intellectual disability, microcephaly, and seizures. Functional studies demonstrate variants result in reduction in ADARB1 product activity or changes in splicing.
PMID: 10894545 - Homozygous knockout mice presented with siezures and early death, supporting the role of ADARB1 in brain function

This gene has also been added to the Genetic Epilepsy and Intellectual Disability panels with a suggested Green classification at the next major review.

Created: 9 Jul 2020, 11:37 a.m. | Last Modified: 14 Jul 2020, 1:35 p.m.

Panel Version: 2.11

Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal

Phenotypes
Neurodevelopmental disorder with hypotonia, microcephaly, and seizures, 618862

Publications

• 32220291
• 32719099