Parkinson Disease and Complex Parkinsonism
Gene: PRKRA
Biallelic mutations cause early-Onset Generalized dystonia-parkinsonism (DYT16), non-responsive to levo-dopa. PMID: 26990861 (1 family, 3 affected with childhood onset generalized dystonia with mild parkinsonian signs including bradykinesia, cognitive impairment); 25737287 (1 brazilian family comp het with early onset pure dystonia); 25142429 (1 polish family with early-onset generalized dystonia and mild parkinsonism), 18243799 (2 unrelated families with young onset generalised dystonia with some parkinsonism). Keep this gene in both this gene to both the dystonia panel and pd.Created: 14 Dec 2016, 5:27 p.m.
Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal
Phenotypes
early-onset generalized dystonia-parkinsonism (DYT16), non-responsive to levo-dopa
Publications
Comment on list classification: I think there seems to be enough evidence for this gene, but it is red on the Early onset dystonia Version 1.0 gene panel.Created: 3 Nov 2016, 3:29 p.m.
19th Dec 2016: panel revised according to expert review and further curation.
This gene has been classified as Green List (High Evidence).
Phenotypes for PRKRA were set to Early Onset Complex Disease; Early-Onset Generalized Dystonia-Parkinsonism; Dystonia 16; early-onset generalized dystonia-parkinsonism (DYT16), non-responsive to levo-dopa
This gene has been classified as Green List (High Evidence).
This gene has been classified as Amber List (Moderate Evidence).
This gene has been classified as Amber List (Moderate Evidence).
Publications for PRKRA were set to 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"; 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; 25914261; 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; 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); 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; 18420150 - a novel heterozygous variant c.266_267delAT; p.H89fsX20 was reported in a proband with early childhood-onset leg dystonia (though testing in the parents was not mentioned).
Publications for PRKRA were set to 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 dystoniaparkinsonism compatible with autosomal recessive inheritance"; 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; 25914261; 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; 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); 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; 18420150 - a novel heterozygous variant c.266_267delAT; p.H89fsX20 was reported in a proband with early childhood-onset leg dystonia (though testing in the parents was not mentioned).
Publications for PRKRA were set to 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 dystoniaparkinsonism compatible with autosomal recessive inheritance"; 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; 25914261; 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; 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); 24142417 - Compound heterozygous variants were reported in a patient with early onset dystonia c.665C>T (p.P222L) inherited from his mother, c.637T>C (p.C213R) was a novel mutation; 18420150 - a novel heterozygous variant c.266_267delAT; p.H89fsX20 was reported in a proband with early childhood-onset leg dystonia (though testing in the parents was not mentioned).
Publications for PRKRA were set to 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 dystoniaparkinsonism compatible with autosomal recessive inheritance"; 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; 25914261; 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; 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); 24142417 - Compound heterozygous variants were reported in a patient with early onset dystonia c.665C>T (p.P222L) inherited from his mother, c.637T>C (p.C213R) was a novel mutation; 18420150
Publications for PRKRA were set to 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 dystoniaparkinsonism compatible with autosomal recessive inheritance"; 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; 25914261; 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; 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); 24142417 - Compound heterozygous variants were reported in a patient with early onset dystonia c.665C>T (p.P222L) inherited from his mother, c.637T>C (p.C213R) was a novel mutation.
Publications for PRKRA were set to 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 dystoniaparkinsonism compatible with autosomal recessive inheritance"; 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; 25914261; 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; 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).
Publications for PRKRA were set to 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 dystoniaparkinsonism compatible with autosomal recessive inheritance"; 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; 25914261; 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.
Phenotypes for PRKRA were set to Early Onset Complex Disease; Early-Onset Generalized Dystonia-Parkinsonism;Dystonia 16
Phenotypes for PRKRA were set to Early Onset Complex Disease;Early-Onset Generalized Dystonia-Parkinsonism
Publications for PRKRA were set to 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 dystoniaparkinsonism compatible with autosomal recessive inheritance".
Publications for PRKRA were set to PMID: 26990861 - c.665C>T homozygous variant was identified in 3 affected siblings (heterozygous in the 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 dystoniaparkinsonism compatible with autosomal recessive inheritance".
PRKRA was added to Parkinson Disease and Complex Parkinsonismpanel. Sources: Expert
PRKRA was created by ellenmcdonagh