Dilated Cardiomyopathy and conduction defectsGene: IDH2
D-2-hydroxyglutaric aciduria 2 OMIM:613657
Created: 25 Mar 2019, 4:30 p.m.
A feature can be dilated cardiomyopathy. Nota (J Med Genet. 2013 Nov;50(11):754-9. doi: 10.1136/jmedgenet-2013-101961) - two paediatric cases where first signs picked up prenatally on ultrasound, one of the two died of cardiac failure age 8 years. Kranendijk J Med Genet. 2013 Nov;50(11):754-9. doi: 10.1136/jmedgenet-2013-101961. - Variant at 140 assoc with this disorder. Note on HGMD only two variants in same nucleotide described. Akbay states cardiomyopathy requiring treatment is frequently observed in type II D2HGA patients (Kranendijk et al. 2010b, 2012). Note: 14 patients described in Kranendijk 2010 - 13 arisen denovo for the same variant Arg140Gln and also reported Arg140Gly in a patient.
Created: 25 Mar 2019, 4:27 p.m.
Paediatric onset only - paediatric panel
Created: 25 Mar 2019, 4:24 p.m.
Mode of inheritance
MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Not fully reviewed however doesn't appear to be associated with primary non-syndromic teen/adult onset DCM.
Created: 17 Jan 2019, 5:41 p.m.
Comment on mode of inheritance: Changed from 'other' to monoallelic, due to reports of heterozygous variants to enable variants in this gene to be tiered.
Created: 5 May 2017, 7:40 a.m.
Comment on mode of inheritance: >3 cases including PMID:20847235 who detected heterozygous germline variants in IDH2 that alter Arg140 in 15 unrelated patients with MIM:613657; in 14 cases the variant was de novo. The mother of 1 patient demonstrated germline mosaicism. PMID:24049096 also report a heterozygous IDH2 and the unaffected mother was a mosaic carrier. Somatic variants also reported.
Created: 20 Mar 2017, 12:23 p.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, 12:22 p.m.
Mode of inheritance
D-2-hydroxyglutaric aciduria 2 613657
Source South West GLH was added to IDH2. Mode of inheritance for gene IDH2 was changed from MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Source Wessex and West Midlands GLH was added to IDH2. Rating Changed from Green List (high evidence) to Green List (high evidence)
Mode of inheritance for IDH2 was changed to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Publications for IDH2 were set to 20847235;24049096
Mode of inheritance for IDH2 was changed to Other - please specifiy in evaluation comments
This gene has been classified as Green List (High Evidence).
IDH2 was created by sleigh
IDH2 was added to Dilated Cardiomyopathy and conduction defectspanel. Sources: Expert Review