Adult onset dystonia, chorea or related movement disorder
Gene: PRKRACopied and removed from publications field:
- PMID: 18420150 - a novel heterozygous variant c.266_267delAT identified in a patient with generalised dystonia
- PMID: 26990861 - c.665C>T homozygous variant was identified in 3 affected siblings with Early-Onset Generalized Dystonia-Parkinsonism (and was heterozygous in the unaffected patients and an unaffected sibling). It was confirmed by Sanger sequencing and had a frequency of 0.01% in the Exome Aggregation Consortium database, predicted to be deleterious by 2 of 6 in silico tools. They showed it was within a founder haplotype shared by all previously reported cases. The authors state screening of PRKRA is warranted in all patients with early-onset generalized dystonia, or dystonia parkinsonism compatible with autosomal recessive inheritance
- PMID: 25737287 Compound het variants (c.G230C (p.Cys77Ser), and in exon 7, c.G638T (p.Cys213Phe)) identified in the two affected siblings reported with dystonia without parkinsonism, unaffected family members were heterozygous
25142429 In a Polish family, the homozygous p.Pro222Leu mutation segregated with autosomal-recessive, early-onset generalized dystonia and slight parkinsonism
- PMID: 18243799 - two unrelated families with members with an apparent autosomal recessive, novel, young-onset, generalised form of dystonia parkinsonism. A region of homozygosity was found in all affected individuals, and narrowed down to the homozygous variant c.665C>T (P222L)
- PMID: 22842711 - describes the clinical features of three original cases with homozygous PRKRA variants - the patients presented with either a pure generalised dystonia or with a dystonia-parkinsonism that was relatively unresponsive to L-dopa
- PMID: 24142417 - Compound heterozygous variants were reported in a patient with early onset dystonia c.665C>T (p.P222L) inherited from his mother, and c.637T>C (p.C213R) was a novel mutationCreated: 29 Mar 2021, 2:11 p.m. | Last Modified: 29 Mar 2021, 2:12 p.m.
Panel Version: 1.75
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.
Publications for gene: PRKRA were set to 24142417; 22842711; 26990861; 25142429; 18420150 - a novel heterozygous variant c.266_267delAT; PMID: 26990861 - c.665C>T homozygous variant was identified in 3 affected siblings with Early-Onset Generalized Dystonia-Parkinsonism (and was heterozygous in the unaffected patients and an unaffected sibling). It was confirmed by Sanger sequencing and had a frequency of 0.01% in the Exome Aggregation Consortium database, predicted to be deleterious by 2 of 6 in silico tools. They showed it was within a founder haplotype shared by all previoulsy reported cases. The Authors state Screening of PRKRA is warranted in all patients with early-onset generalized dystonia, or dystonia parkinsonism compatible with autosomal recessive inheritance; p.H89fsX20 was reported in a proband with early childhood-onset leg dystonia (though testing in the parents was not mentioned).; 25737287; 25737287 Compound het variants (c.G230C (p.Cys77Ser), and in exon 7, c.G638T (p.Cys213Phe)) identified in the two affected siblings reported with dystonia without parkinsonism, unaffected family members were heterozygous; 25142429 In a Polish family, the homozygous p.Pro222Leu mutation segregated with autosomal-recessive, early-onset generalized dystonia and slight parkinsonism; 18420150; 18243799 - two unrelated families with members with an apparent autosomal recessive, novel, young-onset, generalised form of dystonia parkinsonism. A region of homozygosity was found in all affected individuals, and narrowed down to the homozygous variant c.665C>T (P222L); 22842711 describes the clinical features of three original cases with homozygous PRKRA variants - the patients presented with either a pure generalised dystonia or with a dystonia-parkinsonism that was relatively unresponsive to L-dopa; http://www.ncbi.nlm.nih.gov/books/NBK1155/; 24142417 - Compound heterozygous variants were reported in a patient with early onset dystonia c.665C>T (p.P222L) inherited from his mother, and c.637T>C (p.C213R) was a novel mutation; 18243799; 25914261
Phenotypes for gene: PRKRA were changed from Early-Onset Generalized Dystonia-Parkinsonism; Early Onset Complex Disease; Dystonia 16; early-Onset Generalized dystonia-parkinsonism (DYT16), non-responsive to levo-dopa; early-onset generalized dystonia-parkinsonism (DYT16), non-responsive to levo-dopa; Dystonia; Dystonia 16, 612067 to Dystonia 16, OMIM:612067
Source NHS GMS was added to PRKRA.
Source London North GLH was added to PRKRA.
gene: PRKRA was added gene: PRKRA was added to Adult onset movement disorder. Sources: Expert Review Green Mode of inheritance for gene: PRKRA was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: PRKRA were set to 24142417; 22842711; 26990861; 25142429; 18420150 - a novel heterozygous variant c.266_267delAT; PMID: 26990861 - c.665C>T homozygous variant was identified in 3 affected siblings with Early-Onset Generalized Dystonia-Parkinsonism (and was heterozygous in the unaffected patients and an unaffected sibling). It was confirmed by Sanger sequencing and had a frequency of 0.01% in the Exome Aggregation Consortium database, predicted to be deleterious by 2 of 6 in silico tools. They showed it was within a founder haplotype shared by all previoulsy reported cases. The Authors state Screening of PRKRA is warranted in all patients with early-onset generalized dystonia, or dystonia parkinsonism compatible with autosomal recessive inheritance; p.H89fsX20 was reported in a proband with early childhood-onset leg dystonia (though testing in the parents was not mentioned).; 25737287; 25737287 Compound het variants (c.G230C (p.Cys77Ser), and in exon 7, c.G638T (p.Cys213Phe)) identified in the two affected siblings reported with dystonia without parkinsonism, unaffected family members were heterozygous; 25142429 In a Polish family, the homozygous p.Pro222Leu mutation segregated with autosomal-recessive, early-onset generalized dystonia and slight parkinsonism; 18420150; 18243799 - two unrelated families with members with an apparent autosomal recessive, novel, young-onset, generalised form of dystonia parkinsonism. A region of homozygosity was found in all affected individuals, and narrowed down to the homozygous variant c.665C>T (P222L); 22842711 describes the clinical features of three original cases with homozygous PRKRA variants - the patients presented with either a pure generalised dystonia or with a dystonia-parkinsonism that was relatively unresponsive to L-dopa; http://www.ncbi.nlm.nih.gov/books/NBK1155/; 24142417 - Compound heterozygous variants were reported in a patient with early onset dystonia c.665C>T (p.P222L) inherited from his mother, and c.637T>C (p.C213R) was a novel mutation; 18243799; 25914261 Phenotypes for gene: PRKRA were set to Early-Onset Generalized Dystonia-Parkinsonism; Early Onset Complex Disease; Dystonia 16; early-Onset Generalized dystonia-parkinsonism (DYT16), non-responsive to levo-dopa; early-onset generalized dystonia-parkinsonism (DYT16), non-responsive to levo-dopa; Dystonia; Dystonia 16, 612067