Dystonia - complex

Gene: GLB1

Green List (high evidence)

Established gene-disease association with dystonia a presenting feature in chronic/adult onset GM1-gangliosidosis.

PMID: 24156116 - Lysosomal storage disorder characterised by neurodegeneration and mild skeletal changes that is represented by a spectrum - severe, intermediate and mild.
Dystonia typically presents in late childhood to third decade in individuals with a milder form of gangliosidosis.

PMID: 35937492 - mild kyphoscoliosis and visual impairment. She developed generalised dystonia along with other neurological features.
Genetic testing identified compound het mutation (Thr82Met; His112Pro) - both present in gnomAD v4.1 at a rare enough FAF for AR condition.

PMID: 34514040 - Individual presenting with dystonia, cognitive impairment and other neurological features. Older brother presented with dystonia as well but had a milder phenotype. Both siblings also present with concordant MRI findings suggestive of gangliosidosis.
Both siblings had homozygous p.Phe107Leu mutation.

PMID: 1353343 - Multiple unrelated Japanese individuals with GM1 gangliosidosis. Affected individuals presented with gait and speech disturbances along with muscle hypotonia and dystonic posturing.
Ile51Thr missense variant was identified homozygous state in all but one patient.
One patient was compound heterozygous (Ile51Thr;Arg457Gln)

Created: 9 Dec 2024, 9:34 p.m. | Last Modified: 9 Dec 2024, 9:34 p.m.

Panel Version: 0.254

Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal

Phenotypes
GM1 gangliosidosis type 3 MONDO:0009262

Publications

• 24156116
• 35937492
• 34514040
• 1353343