Variants in the CSTB gene have been reported in more than 55 affected individuals (from 40 families) with autosomal recessive (AR) Unverricht – Lundborg disease (aka EPM1 (Epilepsy, progressive myoclonic)) since 1996 (Pennacchio et al.). Most of affected individuals have repeat expansion variants, which is proved to cause a loss of function of the protein and it suggest homozygous loss of function is the mechanism of Unverricht – Lundborg disease for this gene. This gene-disease relationship is supported by expression study, and animal model study. In summary, CSTB is definitively associated with autosomal recessive Unverricht – Lundborg disease. This has been repeatedly demonstrated in both the research and clinical diagnostic setting, and has been upheld over time. This classification was approved by the ClinGen Epilepsy Gene Curation Expert Panel by 6/16/2020.
Lumping and Splitting: Per criteria outlined by the ClinGen Lumping and Splitting Working Group, we found differences in phenotypic variability between three disease entities: (1) Unverricht – Lundborg syndrome(EPM1) (MONDO:0009698), and (2) developmental and epileptic encephalopathy (MONDO:0100062). Therefore, we have split curations for the disease entities, (1) Unverricht – Lundborg syndrome(EPM1) (MONDO:0009698), and (2) developmental and epileptic encephalopathy (MONDO:0100062).
The GenCC data are available free of restriction under a CC0 1.0 Universal (CC0 1.0) Public Domain Dedication. The GenCC requests that you give attribution to GenCC and the contributing sources whenever possible and appropriate. The accepted Flagship manuscript is now available from Genetics in Medicine (https://www.gimjournal.org/article/S1098-3600(22)00746-8/fulltext).
The information on this website is not intended for direct diagnostic use or medical decision-making without review by a genetics professional. Individuals should not change their health behavior solely on the basis of information contained on this website. The GenCC does not independently verify the submitted information. Though the information is obtained from sources believed to be reliable, no warranty, expressed or implied, is made regarding accuracy, adequacy, completeness, reliability or usefulness of any information. This disclaimer applies to both isolated and aggregate uses of the information. The information is provided on an "as is" basis, collected through periodic submission and therefore may not represent the most up-to-date information from the submitters. If you have questions about the medical relevance of information contained on this website, please see a healthcare professional; if you have questions about specific gene-disease claims, please contact the relevant sources; and if you have questions about the representation of the data on this website, please contact gencc@thegencc.org.