Hereditary neuropathy NOT PMP22 copy numberGene: POLR3B
Comment on list classification: New gene added by Zornitza Stark (Australian Genomics). Djordjevic et al. 2021 (PMID:33417887) identified different de novo POLR3B variants in 6 unrelated individuals. EMG/NCSs for 5/6 individuals revealed predominantly demyelinating sensory and motor neuropathy. Other features included ID, ataxia, spasticity.
POLR3B is listed in G2P with a 'probable' disease confidence rating for this phenotype (POLR3B-related neurodevelopmental disorder - monoallelic), but is not yet in OMIM.
Overall, there is sufficient evidence to warrant a Green rating on this panel.
Created: 16 Jun 2021, 1:04 p.m. | Last Modified: 16 Jun 2021, 1:04 p.m.
Panel Version: 1.26
Note biallelic variants cause a leukodystrophy.
New MOI and new phenotype reported in PMID: 33417887: Six unrelated individuals with de novo missense variants and ataxia, spasticity, variable intellectual disability and epilepsy, and predominantly demyelinating sensory motor peripheral neuropathy.
Protein modeling and proteomic analysis shows variants caused aberrant association of individual enzyme subunits rather than affecting overall enzyme assembly or stability.
Created: 1 Feb 2021, 10:50 a.m.
Mode of inheritance
MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Ataxia, spasticity, and demyelinating neuropathy
Phenotypes for gene: POLR3B were changed from Ataxia, spasticity, and demyelinating neuropathy to POLR3B-related neurodevelopmental disorder; Ataxia, spasticity, and demyelinating neuropathy
Gene: polr3b has been classified as Amber List (Moderate Evidence).
Tag Q2_21_rating tag was added to gene: POLR3B.
gene: POLR3B was added gene: POLR3B was added to Hereditary neuropathy NOT PMP22 copy number. Sources: Literature Mode of inheritance for gene: POLR3B was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted Publications for gene: POLR3B were set to 33417887 Phenotypes for gene: POLR3B were set to Ataxia, spasticity, and demyelinating neuropathy Review for gene: POLR3B was set to GREEN