Hereditary neuropathy or pain disorder

Gene: TUBB3

Green List (high evidence)

The rating of this gene has been updated to green following NHS Genomic Medicine Service approval.

Created: 24 Feb 2025, 5:02 p.m. | Last Modified: 24 Feb 2025, 5:02 p.m.

Panel Version: 6.148

Mode of inheritance
MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted

Comment on list classification: Peripheral neuropathy has been reported >3 unrelated cases with CFEOM3A and one family with multiple mutant carriers had isolated peripheral neuropathy (PMID: 20074521). The scope of this panel has now been expanded to complex forms of neuropathy and therefore this gene can be promoted to Green at the next GMS panel update.

Created: 6 Nov 2024, 1:23 p.m. | Last Modified: 6 Nov 2024, 1:23 p.m.

Panel Version: 6.120

I don't know

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, 8:29 p.m. | Last Modified: 6 Dec 2019, 8:29 p.m.

Panel Version: 0.67

Comment on list classification: Gene included in a list of complex neuropathy syndrome genes recommended to be downgraded for R78 panel (list submitted by Alex Rossor 15th July 2019)

Created: 6 Dec 2019, 8:28 p.m. | Last Modified: 6 Dec 2019, 8:28 p.m.

Panel Version: 0.67

Rating and review submitted on behalf of James Polke (Neurogenetics Laboratory,Institute of Neurology, London), on behalf of London North GLH for GMS Neurology specialist test group.

Created: 9 May 2019, 5 p.m.

Green List (high evidence)

Comment on list classification: Gene added by a reviewer, and rated green by a second reviewer. It is a probable DD gene for congenital fibrosis of the extraocular muscles.

Created: 9 May 2016, 10 a.m.

Green List (high evidence)

multiple affected individuals - unrelated - should be includedin R78 now that includes complex phenotypes

Created: 20 Oct 2024, 10:58 a.m. | Last Modified: 20 Oct 2024, 10:58 a.m.

Panel Version: 5.19

CFEOM3A phenotype

Created: 9 Dec 2015, 8:51 a.m.

Mode of inheritance
MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted

Phenotypes
ptosis, ophthalmoplegia, exotropia, facial weakness, facial dysmorphisms, and, in most cases, distal congenital joint contractures, and subsequently develop intellectual disabilities, gait disorders with proximal joint contractures, Kallmann syndrome (hypogonadotropic hypogonadism and anosmia), and a progressive peripheral neuropathy during the first decade of life

Publications

• 34652576 : 25482575

Green List (high evidence)

CFEOM3A phenotype

Created: 8 Dec 2015, 3:07 p.m.

Mode of inheritance
MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted