Early onset or syndromic epilepsy
Gene: DNAJC5As discussed with members of the GMS Neurology Specialist Test Group on the Webex call 22nd November 2019 for Clinical Indication R59 Early onset or syndromic epilepsy: Agreed that there is insufficient evidence to rate this gene Green. Seizures present later. Demoted from Green to Amber.Created: 25 Nov 2019, 9:16 p.m. | Last Modified: 25 Nov 2019, 9:16 p.m.
Panel Version: 1.464
Comment on list classification: Added to panel as a Green gene as seizures are a symptom of the metabolic disorder, and sufficient epilepsy cases from literature.Created: 7 Nov 2019, 10:43 a.m. | Last Modified: 7 Nov 2019, 10:43 a.m.
Panel Version: 1.400
PMID:22235333: Velinov et al., 2012. The authors previously described the Parry family in the 1970s. All affected individuals from the family had a history of progressive seizure disorder. They identified a pLeu116del variant in DNAJC5 which segregated with the disease. 8 additional families were studied for this paper, with seizures amongst the phenotypes. In one affected individual, pLeu115Arg was identified (proband BD-319) who had seizures and gradual dementia beginning in the mid 30s.Created: 7 Nov 2019, 10:28 a.m. | Last Modified: 7 Nov 2019, 10:28 a.m.
Panel Version: 1.399
PMID:29506599: Jarrett et al., 2018 report a family with Kufs disease in which the proband and 3/4 children presented with cognitive impariment, seizures and myoclonus. Genetic testing of all four children was positive for a c.346_348delCTC(p.L116del) variant in the DNAJC5 gene. EEG on the asymptomatic fourth child showed moderatley severe slowing. The proband's father was deceased but had a history of epileptic seizures.Created: 7 Nov 2019, 10:28 a.m. | Last Modified: 7 Nov 2019, 10:28 a.m.
Panel Version: 1.399
PMID:22978711: Cadieux-Dion et al., 2013. report a p.L116del variant in DNAJC5 in two distinct American families, and a p.L115R variant in an additional family. All individuals showed generalized tonic-clonic seizures.Created: 7 Nov 2019, 10:27 a.m. | Last Modified: 7 Nov 2019, 10:27 a.m.
Panel Version: 1.399
Added DNAJC5 to the Epilepsy panel based on a Green rating on the 'Inborn errors of metabolism' panel: seizures are listed as a symptom of MIM:162350 in OMIM.
Sources: Literature, OtherCreated: 7 Nov 2019, 10:27 a.m.
Mode of inheritance
MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Phenotypes
Ceroid lipofuscinosis, neuronal, 4, Parry type, 162350; autosomal dominant Kufs disease; generalized tonic–clonic seizures
Publications
Gene: dnajc5 has been classified as Amber List (Moderate Evidence).
Gene: dnajc5 has been classified as Green List (High Evidence).
gene: DNAJC5 was added gene: DNAJC5 was added to Genetic epilepsy syndromes. Sources: Literature,Other Mode of inheritance for gene: DNAJC5 was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown Publications for gene: DNAJC5 were set to 22978711; 29506599; 22235333 Phenotypes for gene: DNAJC5 were set to Ceroid lipofuscinosis, neuronal, 4, Parry type, 162350; autosomal dominant Kufs disease; generalized tonic–clonic seizures