Ataxia and cerebellar anomalies - narrow panel
Gene: POLR3B
The rating of this gene has been updated to green following NHS Genomic Medicine Service approval.Created: 5 Feb 2023, 5:18 p.m. | Last Modified: 5 Feb 2023, 5:18 p.m.
Panel Version: 3.30
Comment on list classification: New gene added by Zornitza Stark (Australian Genomics). Progressive childhood-onset cerebellar ataxia is a feature in a subset of cases with biallelic variants in this gene. There are sufficient unrelated families in literature to warrant a Green rating on this panel (>10 individuals reported with ataxia)
Recently, heterozygous variants were also linked to ataxia, with different de novo POLR3B variants identified in 6 unrelated individuals (PMID:33417887). All had had a variable degree of gait dysfunction - 5/6 had truncal and/or appendicular ataxia with wide-based ataxic gait, inability to perform tandem gait, or gait instability. Protein modelling and proteomic analysis shows variants caused aberrant association of individual enzyme subunits rather than affecting overall enzyme assembly or stability.
Comment on mode of inheritance: Both biallelic and monoallelic variants have been linked to ataxia - enough evidence for a Green rating for both allelic requirementsCreated: 16 Jun 2021, 11:25 a.m. | Last Modified: 16 Jun 2021, 11:30 a.m.
Panel Version: 2.197
Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal
Publications
Ataxia is a presenting feature.
Sources: Expert listCreated: 12 Sep 2020, 6:51 a.m.
Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal
Phenotypes
Leukodystrophy, hypomyelinating, 8, with or without oligodontia and/or hypogonadotropic hypogonadism, MIM# 614381
Publications
Variants in this GENE are reported as part of current diagnostic practice
Tag Q2_21_rating was removed from gene: POLR3B.
Source Expert Review Green was added to POLR3B. Source NHS GMS was added to POLR3B. Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Phenotypes for gene: POLR3B were changed from Leukodystrophy, hypomyelinating, 8, with or without oligodontia and/or hypogonadotropic hypogonadism, OMIM:614381 to Leukodystrophy, hypomyelinating, 8, with or without oligodontia and/or hypogonadotropic hypogonadism, OMIM:614381; POLR3B-related neurodevelopmental disorder; Ataxia, spasticity, and demyelinating neuropathy
Tag Q2_21_rating tag was added to gene: POLR3B.
Publications for gene: POLR3B were set to 22036171; 22036172
Mode of inheritance for gene: POLR3B was changed from BIALLELIC, autosomal or pseudoautosomal to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Gene: polr3b has been classified as Amber List (Moderate Evidence).
Phenotypes for gene: POLR3B were changed from Leukodystrophy, hypomyelinating, 8, with or without oligodontia and/or hypogonadotropic hypogonadism, MIM# 614381 to Leukodystrophy, hypomyelinating, 8, with or without oligodontia and/or hypogonadotropic hypogonadism, OMIM:614381
gene: POLR3B was added gene: POLR3B was added to Ataxia and cerebellar anomalies - narrow panel. Sources: Expert list Mode of inheritance for gene: POLR3B was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: POLR3B were set to 22036171; 22036172 Phenotypes for gene: POLR3B were set to Leukodystrophy, hypomyelinating, 8, with or without oligodontia and/or hypogonadotropic hypogonadism, MIM# 614381 Review for gene: POLR3B was set to GREEN gene: POLR3B was marked as current diagnostic