Hereditary neuropathy or pain disorder
Gene: PNKP
The rating of this gene has been updated following NHS Genomic Medicine Service approval.Created: 3 Mar 2022, 6:31 p.m. | Last Modified: 3 Mar 2022, 6:31 p.m.
Panel Version: 1.83
Comment on list classification: There is enough evidence for this gene to be rated GREEN at the next major review.Created: 25 Jan 2021, 2:49 p.m. | Last Modified: 25 Jan 2021, 2:49 p.m.
Panel Version: 1.21
Associated with relevant phenotype in OMIM, but not associated with phenotype in Gen2Phen, although variants PNKP have been given a confirmed classification in Gen2Phen for Ataxia-oculomotor apraxia 4 (OMIM:616267). At least 2 variants were reported: rs774995635, was homozygous in 5 affected members of a large Costa Rican family (18 affected members, but only 5 were sequenced) and heterozygous in the mother of one of the affected subjects who was sequenced (PMID 30039206). Compound heterozygous rs774995635 and rs770849181 were reported in five unrelated Costa Rican cases, although it was reported that there appeared to be a ancestral founder haplotype for the rs770849181 (PMID 30039206). A further case was reported where a 17year old with axonal Charcot-Marie-Tooth disease was homozygous and his parents were heterozygous for rs770849181 (PMID 27066567).Created: 25 Jan 2021, 2:48 p.m. | Last Modified: 25 Jan 2021, 2:48 p.m.
Panel Version: 1.19
In PMID: 30039206 reported a homozygous nonsense variant in a large Costa Rican family segregating with CMT2 phenotype. Additional 5 cases with compound heterozygous nonsense variants and CMT2 phenotype also reported. Some patients have Ataxia, but not oculomotor apraxia or Microcephaly, seizures, and developmental delay.Created: 13 Jan 2021, 6:41 a.m. | Last Modified: 13 Jan 2021, 6:41 a.m.
Panel Version: 1.19
Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal
Phenotypes
Polyneuropathy; ataxia
Publications
Variants in this GENE are reported as part of current diagnostic practice
Gene rated Amber : From feedback from Genomics England Clinical team (Anna de Burca and Meriel McEntagart): Extension of panel scope but limited evidence / Broader phenotype: good evidence for ataxia/oculomotor apraxia, less for more severe phenotypeCreated: 7 Dec 2019, 12:03 a.m. | Last Modified: 7 Dec 2019, 12:03 a.m.
Panel Version: 0.86
This gene has changed ratings because the panel for R78 was going to be a broad panel (to include conditions where neuropathy is part of a more complex phenotype or where there is overlap with another neurological presentation eg. HSP) but subsequently during the follow up call on 21st June with the Test Group it was agreed that it was more clinically relevant for R78 to be restricted to genes that are associated with isolated neuropathy, which this panel represents. For genes that represent the broader phenotype see https://panelapp.genomicsengland.co.uk/panels/85/.Created: 6 Dec 2019, 10:25 p.m. | Last Modified: 6 Dec 2019, 10:25 p.m.
Panel Version: 0.84
Review and rating uploaded from file (Curation_Template_GMS_Neuro_AR_20190521.xlsx) submitted by Alex Rossor (UCL Institute of Neurology) on behalf of London North GLH for GMS Neurology specialist test group.Created: 11 Jun 2019, 1:40 p.m.
Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal
Phenotypes
Microcephaly, global developmental delay, progressive cerebellar ataxia and atrophy, sensory-motor axonal neuropathy
Publications
Tag for-review was removed from gene: PNKP.
Source Expert Review Green was added to PNKP. Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Tag for-review tag was added to gene: PNKP.
Gene: pnkp has been classified as Amber List (Moderate Evidence).
Publications for gene: PNKP were set to 30039206
Source Expert Review Amber was added to PNKP. Rating Changed from Red List (low evidence) to Amber List (moderate evidence)
gene: PNKP was added gene: PNKP was added to Hereditary neuropathy NOT PMP22 copy number. Sources: NHS GMS,London North GLH Mode of inheritance for gene: PNKP was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: PNKP were set to 30039206 Phenotypes for gene: PNKP were set to Microcephaly, global developmental delay, progressive cerebellar ataxia and atrophy, sensory-motor axonal neuropathy; Microcephaly, seizures, and developmental delay, 613402; Ataxia-oculomotor apraxia 4, 616267