Early onset or syndromic epilepsy
Gene: ADPRHL2Added new-gene-name tag, new approved HGNC gene symbol for ADPRHL2 is ADPRSCreated: 18 Dec 2019, 4:48 p.m. | Last Modified: 18 Dec 2019, 4:48 p.m.
Panel Version: 2.0
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
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
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.
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
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
Variants in this GENE are reported as part of current diagnostic practice
Publications for gene: ADPRHL2 were set to 30100084
Phenotypes for gene: ADPRHL2 were changed from Intellectual disability, cerebellar atrophy, ataxia and epilepsy to Neurodegeneration, childhood-onset, stress-induced, with variable ataxia and seizures OMIM:618170; neurodegeneration, childhood-onset, stress-induced, with variable ataxia and seizures MONDO:0100095
Tag new-gene-name tag was added to gene: ADPRHL2.
Source Wessex and West Midlands GLH was added to ADPRHL2.
Source NHS GMS was added to ADPRHL2.
Zornitza Stark: 6 families recently reported w
Gene: adprhl2 has been classified as Green List (High Evidence).
Publications for gene: ADPRHL2 were set to DOI:https://doi.org/10.1016/j.ajhg.2018.07.010
Gene: adprhl2 has been classified as Green List (High Evidence).
ADPRHL2 was added to Genetic Epilepsy Syndromes panel. Sources: Literature
ADPRHL2 was created by Zornitza Stark