No evidence of a role for cystatin B gene in juvenile myoclonic epilepsy

Abstract

Laura Mumoli is a postdoctoral fellow with special interest in epilepsy. SUMMARYGenetic factors play a major role in the etiology of juvenile myoclonic epilepsy (JME), a common form of idiopathic generalized epilepsy, but so far, genes related to JME remain largely unknown. JME shares electroclinical features with Unverricht-Lundborg disease (progressive myoclonic epilepsy type 1; EPM1), a form of progressive myoclonus epilepsy characterized by myoclonus, epilepsy, and gradual neurologic deterioration. EPM1 is caused by mutations in the gene that codes for cystatin B (CSTB), an inhibitor of cysteine protease. In the present study, we wished to investigate the role of the CSTB gene in patients with JME. Fifty-seven unrelated patients (35 women; mean age AE standard deviation [SD], 24.1 AE 7.7; mean age AE SD at onset, 15.3 AE 2.4) with JME were enrolled. Twenty-three of 57 patients were the probands of families with JME. The molecular diagnosis was carried out to identify the common dodecamer repeat expansion mutation or other disease-causing mutations in the CSTB gene. The molecular analysis did not depict mutations in any of the 57 patients with JME. Our study did not support a role for the CSTB gene in patients with familial or sporadic JME.

A novel c132‐134del mutation in Unverricht‐Lundborg disease and the review of literature of heterozygous compound patients

“…They described a case of a compound heterozygous female patient affected by a mild phenotype that was mistaken for juvenile myoclonic epilepsy (genotype screening was performed for a distant family history of EPM1). It is worth noting that CSTB mutations were never found in juvenile myoclonic epilepsy . On these data we speculate that in heterozygous compound patients an association of genetic and gender‐specific factors can reduce the efficacy of residual Cystatin B (to counteract damages resulting from endogenous protease activity).…”

“…It is worth noting that CSTB mutations were never found in juvenile myoclonic epilepsy. 8 On these data we speculate that in heterozygous compound patients an association of genetic and gender-specific factors can reduce the efficacy of residual Cystatin B (to counteract damages resulting from endogenous protease activity). Even if a haploinsufficiency of CSTB seems to not affect heterozygous compound patients, 5 a functional deficit of mutated protein cannot be excluded.…”

Juvenile myoclonic epilepsy phenotype in a family with Unverricht‐Lundborg disease

“…This clinical presentation could be more frequent in Tunisia than in European countries since it was shown that the course of the disease is more severe in Northern Europe than in Maghreb (Gargouri-Berrechid et al, 2016). In addition, Laura Mumoli and colleagues showed an absence of mutation associated with ULD in 33 unrelated patients with JME from Italy (Mumoli et al, 2015). The size of repeats in Family 1 was within the classic range and even larger than that of Family 2, which does not account for the very mild phenotype.…”

Unverricht‐Lundborg disease

“…Although ULD remains uncommon, it has been increasingly diagnosed among patients with drug-resistant myoclonic epilepsy, as shown, for instance, in Holland (de Haan et al, 2004). However, whereas the most common mutation in ULD affects the cystatin B gene (CSTB), no evidence for a role of this gene was found in sporadic or familial cases of juvenile myoclonic epilepsy (JME) (Mumoli et al, 2015). The availability of molecular genetic diagnostic techniques in developed countries has certainly helped.…”