Adult onset movement disorderGene: PRKRA
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.
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