Early onset or syndromic epilepsy

Gene: CSTB

I don't know

Review and rating collated by Tracy Lester (Oxford Medical Genetics Laboratories Oxford University Hospitals NHS Foundation Trust, 2019_02_06) on behalf of Wessex and West Midlands GLH for GMS Neurology specialist test group, for Clinical Indication R59 'Early onset or syndromic epilepsy'. Review contributors: John Taylor and Helen Lord. Suggested gene rating: Green.

Created: 6 Aug 2019, 8:38 p.m. | Last Modified: 6 Aug 2019, 8:38 p.m.

Panel Version: 1.189

Green List (high evidence)

Previously called EPM1. AR progressive myoclonic epilepsy 1A (Unverricht and Lundborg) (EPM1A). Onset of neurodegneration between 6 and 13. Although it is considered a progressive myoclonic epilepsy - it differs as it only appears to be progressive in adolescence and stabilises in early adulthood. Lalioti et al, 1997 - 6 nucleotide changes in the CSTB gene in Non-Finnish EPM1 families - molecular modelling of G4R -predict to affect contact of cystatin B with papain. The 6 mutations werre found in 7/29 unrelated cases -hom in 1, compound het in the rest. Lalioti et al, 1997 - expansions of a 12 mer repeat 70 nt upstream of the transription start site. Normal alleles have 203 copies, whereas mutant alleles contain more than 60 such repeats. See premutation alleles which show marked instability.

Created: 6 Aug 2019, 8:31 p.m. | Last Modified: 6 Aug 2019, 8:31 p.m.

Panel Version: 1.188

Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal

Phenotypes
Epilepsy progressive myoclonic 1A (Unverricht and Lundborg), 254800

Publications

• 8596935
• 17003839

Green List (high evidence)

Comment on list classification: Changing rating to green in agreement with reviews

Created: 18 Oct 2018, 9:28 a.m.

Associated with relevant phenotype in OMIM and as confirmed Gen2Phen gene. At least 6 variants reported in numerous families, including a dodecamer (CCCCGCCCCGCG) repeat expansion in the 5-prime untranslated region CSTB.

Created: 1 Oct 2018, 12:12 p.m.

Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal

Phenotypes
Epilepsy, progressive myoclonic 1A (Unverricht and Lundborg) 254800

Publications

• 28378817
• 21757863
• 15329070
• 9012407

Green List (high evidence)

Multiple patients reported with bi-allelic variants in this gene. Some variants are missense, but there is a common 12bp expansion allele -- detectable by WGS?

Created: 12 Aug 2018, 6:01 a.m.

Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal

Phenotypes
Epilepsy, progressive myoclonic 1A (Unverricht and Lundborg); MIM#254800

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

Red List (low evidence)

Red List (low evidence)

Red List (low evidence)

Red List (low evidence)

Comment on mode of pathogenicity: Nucleotide repeat expansion in some cases. Tagged 5.12.16 by Alice Gardham

Created: 5 Dec 2016, 2:09 p.m.