Early onset or syndromic epilepsy

Gene: ITPA

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

Green List (high evidence)

AR EIEE 35 - onset of seizures in the first few months of life associated with essentially no normal development. Keevalem et al, 2015 - 7 patients from 4 families with severe EIEE, 2 families consang and patients presented shortly after birth with seizures 6/7 died between 10 months and 2.5 years. 4 diff hom mutations identified . The erythrocytes of 1 proband showed severely reduced ITPase activity and accumulation of ITP whereas the other 3 probands showed severely reduced ITPase activity and no accum of ITP. ITPase deficiency is also asociated with variant is n this gene - most commonly P32T.

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

Publications

• 26224535
• 27770805

Green List (high evidence)

Comment on "pharmacogenetic" tag: Abnormal 6-mercaptopurine metabolism in ITPase-deficient patients may cause thiopurine drug toxicity

Created: 20 Mar 2017, 11:13 a.m.

Inclusion of this as a green gene on this panel is appropriate, based on the review in the Undiagnosed metabolic disorders panel and the views of clinical expert, Dr Arianna Tucci, UCL.

Created: 20 Mar 2017, 11:12 a.m.

Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal

Phenotypes
Epileptic encephalopathy, early infantile, 35, 616647