Paroxysmal central nervous system disorders

Gene: CACNB4

I don't know

Associated with EA5 in a single French Canadian family (we currently have this gene in our brain channel panel but have never detected anything other than a VUS). ? Amber.

Created: 1 Oct 2019, 12:20 p.m. | Last Modified: 1 Oct 2019, 12:20 p.m.

Panel Version: 0.158

I don't know

It was red-listed on all the movement disorder panels it had previously been on. Now very limited evidence (if any) for being a causative gene, still a possibility of being some sort of modifier but that isn't what we're looking for.

Created: 29 Sep 2019, 7:52 p.m. | Last Modified: 29 Sep 2019, 7:52 p.m.

Panel Version: 0.156

I don't know

The evidence is very weak. So unless anything has changed recently I would leave out.

Created: 29 Sep 2019, 7:46 p.m. | Last Modified: 29 Sep 2019, 7:46 p.m.

Panel Version: 0.155

I don't know

Green or Amber depending on level of evidence.

Created: 23 Sep 2019, 12:51 p.m. | Last Modified: 23 Sep 2019, 12:51 p.m.

Panel Version: 0.95

Green List (high evidence)

I don't know

Review and rating from Robyn Labrum (University College London Hospitals) was collated (September 30th 2019) on behalf of London North GLH for the GMS Neurology specialist test group for clinical indication R66: Paroxysmal central nervous system disorders. Suggested rating: ? Amber. This review agrees with the recent downgrading of CACNB4 to Amber.

Created: 1 Oct 2019, 12:21 p.m. | Last Modified: 1 Oct 2019, 12:21 p.m.

Panel Version: 0.158

Comment on list classification: Downgraded CACNB4 rating from Green to Amber based on GLH review. The most recent comments from Andrea Nemeth and Jonathan Williams agree that there is only weak evidence to support a gene:disease association. The current evidence comes from PMID:10762541 which reports 1 family (plus another family with epilepsy), and a mouse model.

Created: 29 Sep 2019, 7:54 p.m. | Last Modified: 21 Nov 2019, 9:35 a.m.

Panel Version: 0.173

Reviews by Andrea Nemeth and Jonathan Williams were uploaded (September 29th 2019) on their behalf based on email discussion of these genes to reach a consensus on the rating. Comments were received over email, and I uploaded an Amber review based on their comments.

Created: 29 Sep 2019, 7:53 p.m. | Last Modified: 21 Nov 2019, 9:36 a.m.

Panel Version: 0.173

Review and rating from Penny Clouston (Oxford Medical Genetics Laboratories, Oxford University Hospitals NHS Foundation Trust) was collated (September 19th 2019) on behalf of West Midlands, Oxford and Wessex GLH for the GMS Neurology specialist test group. Re-review of a subset of genes was conducted in September 2019 to reach a rating consensus for clinical indication R66: Paroxysmal central nervous system disorders. A question mark was submitted for the rating because of a question over the level of evidence, therefore I uploaded an Amber review from Penny Clouston.

Created: 23 Sep 2019, 12:53 p.m. | Last Modified: 23 Sep 2019, 12:53 p.m.

Panel Version: 0.96

PMID:10762541. Escayg et al., 2000 report a C104F missense mutation in affected members of a German family with epilepsy, and in a French Canadian family with episodic ataxia type 5 (MIM:613855). The French Canadian family had 5 affected individuals in 3 generations. The proband, after age 20 years, experienced recurrent episodes of vertigo and ataxia that lasted for several hours. The proband's mother had identical episodes of vertigo and ataxia after age 30 years.

Created: 19 Sep 2019, 3:09 p.m. | Last Modified: 19 Sep 2019, 3:09 p.m.

Panel Version: 0.94

Review and rating from James Polke (Neurogenetics Laboratory, Institute of Neurology, London) was collated (February 2019) on behalf of London North GLH for the GMS Neurology specialist test group.

Created: 2 Sep 2019, 2:39 p.m. | Last Modified: 2 Sep 2019, 2:39 p.m.

Panel Version: 0.26

Review and rating from Tracy Lester (Oxford Medical Genetics Laboratories, Oxford University Hospitals NHS Foundation Trust) was collated (February 2019) on behalf of West Midlands, Oxford and Wessex GLH for the GMS Neurology specialist test group.

Created: 2 Sep 2019, 1:39 p.m. | Last Modified: 2 Sep 2019, 1:39 p.m.

Panel Version: 0.23

I don't know

Episodic ataxia - limited evidence?

Created: 2 Sep 2019, 1:30 p.m. | Last Modified: 2 Sep 2019, 1:30 p.m.

Panel Version: 0.22

Mode of inheritance
MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown

Phenotypes
Episodic ataxia, type 5, 613855

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