Genes in panel
STRs in panel
Prev Next

Genetic epilepsy syndromes

Gene: ADPRHL2

Green List (high evidence)

ADPRHL2 (ADP-ribosylhydrolase like 2)
EnsemblGeneIds (GRCh38): ENSG00000116863
EnsemblGeneIds (GRCh37): ENSG00000116863
OMIM: 610624, Gene2Phenotype
ADPRHL2 is in 4 panels

5 reviews

Rebecca Foulger (Genomics England curator)

I don't know

Review and rating collated by Tracy Lester (Oxford Medical Genetics Laboratories Oxford University Hospitals NHS Foundation Trust, 2019_02_06) on behalf of Wessex and West Midlands GLH for GMS Neurology specialist test group, for Clinical Indication R59 'Early onset or syndromic epilepsy'. Review contributors: John Taylor and Helen Lord. Suggested gene rating: Green.
Created: 6 Aug 2019, 8:38 p.m. | Last Modified: 6 Aug 2019, 8:38 p.m.
Panel Version: 1.189

Tracy Lester (Genetics laboratory, Oxford UK)

Green List (high evidence)

AR stress induced childhood onset neurodegeneration with variable ataxia and seizures (CONDSIAS). Onset in first years of life following normal early development. Patients have cyclic episodic deterioration in response to stress such as infection or febril illness. The severity is haighly varaible - some patients develop seizures ealy in life, whereas others present at a later age with muscle weakness, ataxia etc. Ghosh et al, 2018 -6 unrelated families - 5 consang and the other with parents from the same village in Sicily - all had neurodegen disorder apparant in childhood and the stress was infection or seizure. Family 1 - 9 children from the UAE - 7 died between the ages of 2 and 15 - all patients in this family presented with seizures between 1 and 2 years. 7 additional patients from 5 other famlies were identified = - 3 developed generalised seizures the other 4 didn't (of note in family 4, 1 sib had seizures and the other didn't). Hom variants detected - 2 nonsense, 1 fs and 3 missense - affecting highly conserved residues in the ADP-ribosyl-glycohydrolase defic. Expression stidues done in 1 nonsense and 1 missense variant - support pathogenicity. Dhausher et al, 2018 - 12 patients from 8 unrelated families (4 consang) 6/12 had seizures. 5 diff hom variants- 1 missense, 1 nonsense, 2 fs and a splice site. Fibroblast studies done.
Created: 6 Aug 2019, 8:31 p.m. | Last Modified: 6 Aug 2019, 8:31 p.m.
Panel Version: 1.188

Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal

Phenotypes
Neurodegeneration, childhood-onset, stress-induced, with variable ataxia and seizures, 618170

Publications

Sarah Leigh (Genomics England Curator)

Comment when marking as ready: Not associated with phenotype in OMIM or in Gen2Phen. Recent publication reports 6 different variants in affected members of 6 apparently unrelated families. Generalized tonic-clonic seizures were reported in 3/6 families, the seizures were were in response to other illness in one of these families. Supportive animal studies were also presented.
Created: 25 Sep 2018, 1:11 p.m.

Konstantinos Varvagiannis (Other)

I don't know

PMID 30100084 reports on 16 affected individuals from 6 different families, most of them consanguineous (and one possibly distantly-related). All subjects were homozygous for either truncating or missense variants. The authors suggest a similar phenotype of a stress-induced neurodegenerative disorder of variable progression, characterized developmental delay (for few prior to other disease manifestations, for most as a result developmental stagnation or loss of milestones), sudden severe onset of seizures, ataxia with cerebellar atrophy and intellectual disability. Western blot of fibroblasts demonstrated absence of the protein product (ARH3) in affected individuals but not in controls. Phenotype was rescued in Parg27.1 mutant flies after either forced expression of Parg or mis-expression of human ADPRHL2 (Drosophila melanogaster has a single Parg-like gene).

This is the first report of the disorder.
Created: 14 Aug 2018, 10:20 a.m.

Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal

Phenotypes
Developmental regression; Seizures; Ataxia; Intellectual disability

Publications

Zornitza Stark (Australian Genomics)

Green List (high evidence)

6 families recently reported with bi-allelic variants in this gene.
Created: 12 Aug 2018, 6:29 a.m.

Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal

Phenotypes
Intellectual disability, cerebellar atrophy, ataxia and epilepsy

Publications

  • DOI:https://doi.org/10.1016/j.ajhg.2018.07.010

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

Details

Mode of Inheritance
BIALLELIC, autosomal or pseudoautosomal
Sources
  • Wessex and West Midlands GLH
  • NHS GMS
  • Expert Review Green
Phenotypes
  • Intellectual disability, cerebellar atrophy, ataxia and epilepsy
OMIM
610624
Clinvar variants
Variants in ADPRHL2
Penetrance
None
Publications
Panels with this gene

History Filter Activity

6 Aug 2019, Gel status: 3

Added New Source

Rebecca Foulger (Genomics England curator)

Source Wessex and West Midlands GLH was added to ADPRHL2.

6 Aug 2019, Gel status: 3

Added New Source

Rebecca Foulger (Genomics England curator)

Source NHS GMS was added to ADPRHL2.

11 Dec 2018, Gel status: 3

Panel promoted to version 1.0

Sarah Leigh (Genomics England Curator)

Zornitza Stark: 6 families recently reported w

25 Sep 2018, Gel status: 3

Entity classified by Genomics England curator

Sarah Leigh (Genomics England Curator)

Gene: adprhl2 has been classified as Green List (High Evidence).

25 Sep 2018, Gel status: 3

Set publications

Sarah Leigh (Genomics England Curator)

Publications for gene: ADPRHL2 were set to DOI:https://doi.org/10.1016/j.ajhg.2018.07.010

25 Sep 2018, Gel status: 3

Entity classified by Genomics England curator

Sarah Leigh (Genomics England Curator)

Gene: adprhl2 has been classified as Green List (High Evidence).

12 Aug 2018, Gel status: 0

Added New Source

Zornitza Stark (Australian Genomics)

ADPRHL2 was added to Genetic Epilepsy Syndromes panel. Sources: Literature

12 Aug 2018, Gel status: 0

Created

Zornitza Stark (Australian Genomics)

ADPRHL2 was created by Zornitza Stark