Hereditary neuropathy

Gene: PNKP

Green List (high evidence)

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, 2:47 p.m. | Last Modified: 25 Jan 2021, 2:47 p.m.

Panel Version: 1.381

Publications

• 27066567

Green List (high evidence)

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, 6:38 a.m. | Last Modified: 13 Jan 2021, 6:41 a.m.

Panel Version: 1.381

Phenotypes
Polyneuropathy; ataxia

Publications

• PMID: 30039206

Variants in this GENE are reported as part of current diagnostic practice

I don't know

The Neurology Specialist Test Group agreed that this gene was recommended for the WGS panel based on a broader phenotype view to include conditions where neuropathy is part of a more complex phenotype or where there is overlap with another neurological presentation eg. HSP. This panel includes conditions where neuropathy is part of a more complex phenotype or where there is overlap with another neurological presentation. This panel as going to be used for R78, 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 and as a result a new panel was created https://panelapp.genomicsengland.co.uk/panels/846/ for this purpose.

Created: 7 Dec 2019, 6:08 p.m. | Last Modified: 7 Dec 2019, 6:08 p.m.

Panel Version: 1.352

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.

Green List (high evidence)

Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal

Phenotypes
Microcephaly, global developmental delay, progressive cerebellar ataxia and atrophy, sensory-motor axonal neuropathy

Publications

• 30039206