Childhood onset dystonia, chorea or related movement disorder
Gene: TSPOAP1
Not associated with a phenotype in OMIM, Gen2Phen or MONDO. At least three TSPOAP1variants have been reported in three unrelated families. Family members carrying homozygous TSPOAP1 variants have dystonia, intellectual disability and cerebellar atrophy to varying degrees. Motor symptoms were apparent between 11 and 13 years of age for NM_004758: c.2449_2450delinsTG, p.Gln817* and c.538delG, p.Ala180Profs*8, while NM_004758: c.5422G>A, p.Gly1808Ser was from 58 years through to the 60s. Similarly, cognitive impairment was apparent from school age and progressed to moderate to extensive, in the carries of the two terminating TSPOAP1 variants, while those with the missense variant were diagnosed with mild cognitive impairment (PMID: 33539324). In vitro functional studies and mouse models support the association of the TSPOAP1 variants and phenotypes seen in the cases (PMID: 33539324).Created: 13 Jun 2023, 2:36 p.m. | Last Modified: 13 Jun 2023, 3:01 p.m.
Panel Version: 3.12
Comment on list classification: There is enough evidence for this gene to be rated GREEN at the next major review.Created: 13 Jun 2023, 2:16 p.m. | Last Modified: 13 Jun 2023, 2:16 p.m.
Panel Version: 3.12
7 affecteds from 3 families (1 consanguineous)
2x null, 1x missense
Affecteds with the null variants presented with juvenile-onset progressive generalized dystonia, associated with intellectual disability and cerebellar atrophy while those with the missense p.(Gly1808Ser) presented with isolated adult-onset focal dystonia (mild cognitive impairment noted). Mouse model.
Sources: LiteratureCreated: 17 Apr 2021, 8:06 a.m.
Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal
Phenotypes
Dystonia, intellectual disability and cerebellar atrophy
Publications
Tag Q3_23_promote_green tag was added to gene: TSPOAP1.
Tag Q3_23_promote_green was removed from TSPOAP1.
Tag Q3_23_promote_green tag was added to gene: TSPOAP1.
Gene: tspoap1 has been classified as Amber List (Moderate Evidence).
gene: TSPOAP1 was added gene: TSPOAP1 was added to Childhood onset dystonia or chorea or related movement disorder. Sources: Literature Mode of inheritance for gene: TSPOAP1 was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: TSPOAP1 were set to 33539324 Phenotypes for gene: TSPOAP1 were set to Dystonia, intellectual disability and cerebellar atrophy Review for gene: TSPOAP1 was set to GREEN