Hereditary Neuropathy_CMT - isolated

Gene: PCK2

I don't know

A few more reported cases may clarify this possible gene-disease association.
PMID: 36845668 - three patients in two families with biallelic variants in PCK2 and supporting animal model. There are three p.(Ser23Ter) homozygotes reported in gnomAD, but given that the phenotype is not a severe paediatric phenotype and the homozygotes are not in the "healthy control" gnomAD cohorts it is plausible that these individuals could be affected.
DECIPHER Patient: 340038 - complex neurodevelpmental disorder phenotype, but does include sensory neuropathy with a stopgain and splice donor variant confirmed in trans
PMID: 32660061 - a heterozygous missense (Arg553Gln) identified in 2 pedigrees with 4 Shetland sheepdogs affected with paroxysmal exercise-induced dyskinesia.
There are also a couple of labs in ClinVar reporting LoF variants as likely pathogenic and pathogenic, but without any supporting evidence and/or information about the condition the variants are curated against.

Created: 3 Mar 2023, 5:57 a.m. | Last Modified: 3 Mar 2023, 5:57 a.m.

Panel Version: 1.699

Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal

Phenotypes
Peripheral neuropathy (MONDO#0005244), PCK2-related

Publications

• 36845668

Red List (low evidence)

HGG journal
https://doi.org/10.1016/j.xhgg.2023.100182

2 families with 3 affected
1x chet missense + p.(Ser23Ter) which has 3 homs in gnomad v3_non_v2+v2)
1x hom NMD-predicted

all 3 patients have weakness and abnormal gait, abnormal conduction studies.
absence of PCK2 protein and profound reduction in activity in fibroblasts
KO mice displayed abnormal nerve conduction studies and peripheral nerve pathology

Created: 2 Feb 2023, 3:40 a.m. | Last Modified: 2 Feb 2023, 3:40 a.m.

Panel Version: 1.632

Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal

Phenotypes
peripheral neuropathy (MONDO#0005244), PCK2-related

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

Red List (low evidence)

Note OMIM reported gene disease association with PEPCK deficiency, mitochondrial - MIM#261650
No published evidence identified supporting this.

Created: 11 Apr 2022, 6:50 a.m. | Last Modified: 11 Apr 2022, 6:50 a.m.

Panel Version: 0.12855

Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal

Phenotypes
PEPCK deficiency, mitochondrial - MIM#261650