Adult onset dystonia, chorea or related movement disorder
Gene: AP1S2Comment on mode of inheritance: Changed MOI from 'XL, biallelic in females' to 'XL, monoallelic in females'.
Review of literature did not reveal any confirmed affected females. Female carriers of AP1S2 variants are phenotypically normal and have mostly shown random X-inactivation. Huo et al., 2019 (PMID: 30714330) state that they identified a female patient (I-1) but this individual was not available for genetic testing and so it is unclear whether they harboured a variant on a one or both alleles.
As no confirmed female cases have been reported and the allelic requirement remains elusive, the MOI should be set to the default XL (i.e. monoallelic in females may cause disease) as this will ensure that both mono and biallelic variants are picked up in females.Created: 18 Oct 2021, 11:53 a.m. | Last Modified: 18 Oct 2021, 11:53 a.m.
Panel Version: 1.125
Changed rating from Green to Red - As agreed by GMS Neurology specialist test group. Classified Red due to their age of onset or do not fit the phenotype.Created: 13 Aug 2019, 11:57 a.m. | Last Modified: 13 Aug 2019, 11:57 a.m.
Panel Version: 0.100
Uploaded an updated Review and rating from a file sent by Robyn Labrum (London North GLH) after webex call 26th July : R56 Adult onset dystonia, chorea or related movement disorder Panel - RED genes from LNGLH_30.07.19.xlsx. To be discussed at next GMS Neurology specialist test group webex September 2019Created: 13 Aug 2019, 11:48 a.m. | Last Modified: 13 Aug 2019, 11:48 a.m.
Panel Version: 0.99
Review and rating submitted by James Polke (North Bristol NHS Trust), unless specified in the review comment, on behalf of London North GLH for GMS Neurology specialist test group.Created: 23 Apr 2019, 1:19 p.m.
Further follow up review by Robyn Labrum (London North GLH) after webex call 26th July 2019 : confirming Red review: onset in infancy - mental retardation syndromeCreated: 13 Aug 2019, 11:38 a.m. | Last Modified: 13 Aug 2019, 11:38 a.m.
Panel Version: 0.98
Comment on list classification: This gene is Green on the Structural basal ganglia disorders v1.10 panel.Created: 3 Jan 2019, 3:13 p.m.
Mode of inheritance for gene: AP1S2 was changed from X-LINKED: hemizygous mutation in males, biallelic mutations in females to X-LINKED: hemizygous mutation in males, monoallelic mutations in females may cause disease (may be less severe, later onset than males)
Phenotypes for gene: AP1S2 were changed from Mental retardation, X-linked syndromic 5 304340; Dystonia to Pettigrew syndrome, OMIM:304340
Source Expert Review Red was added to AP1S2. Rating Changed from Green List (high evidence) to Red List (low evidence)
Source NHS GMS was added to AP1S2.
Source London North GLH was added to AP1S2. Rating Changed from Green List (high evidence) to Green List (high evidence)
Gene: ap1s2 has been classified as Green List (High Evidence).
Source Expert Review Red was added to AP1S2. Added phenotypes Dystonia for gene: AP1S2 Rating Changed from Green List (high evidence) to Red List (low evidence)
gene: AP1S2 was added gene: AP1S2 was added to Adult onset movement disorder. Sources: Expert Review Green Mode of inheritance for gene: AP1S2 was set to X-LINKED: hemizygous mutation in males, biallelic mutations in females Publications for gene: AP1S2 were set to 17617514; 18428203; 23756445 Phenotypes for gene: AP1S2 were set to Mental retardation, X-linked syndromic 5 304340