Early onset dystonia

Gene: DLAT

Comment on list classification: 3 unrelated cases with plausible disease causing variants in the DLAT gene. All cases show dystonia in childhood.

Created: 20 Dec 2018, 9:21 a.m.

Associated with Pyruvate dehydrogenase E2 deficiency in OMIM and Gene2Phenotype with Dystonia, episodic listed as a clinical feature in OMIM.

PMID: 20022530 - McWilliam et al (2010) -two sisters with early onset episodic dystonia and pyruvate dehydrogenase deficiency caused by defects in the E2 subunit. They were compound heterozygotes for two mutations in the DLAT gene. Parents were each carriers for one mutation. One is a nonsense mutation in exon 3, the other is an unusual base substitution 7 bp downstream from a 5′ donor splice site which results in exon 6 being skipped in some transcripts.

PMID: 16049940 - Head et al (2005) - two unrelated patients who are homozygous for different mutations in the DLAT gene for the E2 subunit - a deletion of a glutamic acid residue in the outer lipoyl domain of the protein, and a missense mutation that leads to substitution of leucine for phenylalanine in the catalytic site. Both showed dystonia in childhood.

Created: 19 Dec 2018, 5:53 p.m.

I don't know

3 unrelated individuals with dystonia secondary to a metabolic disorder
McWilliam (2010, 20022530), Two sisters with early onset episodic dystonia and pyruvate dehydrogenase deficiency caused by defects in the E2 subunit. Both have neuroimaging features similar to previously described patients and have mutations in the DLAT gene.
Head (2005, 16049940). 2 unrelated individuals from consanginious families with homozygous DLAT variants and pyruvate dehydrogenase deficiency.

Created: 7 Dec 2018, 4:41 p.m.

Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal

Phenotypes
episodic dystonia; pyruvate dehydrogenase deficiency

Publications

• 20022530
• 16049940