title: A novel c132-134del mutation in Unverricht-Lundborg disease and the review of literature of heterozygous compound patients.
abstract: Unverricht-Lundborg disease or progressive myoclonic epilepsy type 1 (EPM1) is an autosomal recessive disease caused by mutation of the cystatin B gene (CSTB), located on chromosome 21q22.3. The most common mutation is an expansion of unstable dodecamer repetition (CCCCGCCCCGCG), whereas other types of mutations are rare. Among these, heterozygous compound mutations are described to induce a more severe phenotype than that of homozygous dodecameric repetition. We report two siblings affected by heterozygous compound mutations carrying a novel mutation of the deletion of three nucleotides in exon 2 of the gene in position 132-134 of the coding sequence (c.132-134del) in the allele not including the dodecamer repetition. This mutation results in the loss of two amino acid residues and insertion of an asparagine in position 44 (p.Lys44_Ser45delinsAsn). Our patients presented a very different clinical picture. The male patient had a severe myoclonus, drug-resistant epilepsy and psychiatric comorbidity, while his affected sister had only very rare seizures and sporadic myoclonic jerks at awakening. The revision of literature about heterozygous compound EPM1 patients confirms this gender phenotypic expressivity, with female patients carrying less severe symptoms than male patients. These data lead to the hypothesis of complex gender-specific factors interacting with CSTB expressivity in EPM1 patients.
authors.affiliation: Clinical Neurology, Campus Biomedico University of Rome, Rome, Italy.
authors.forename: Giovanni
authors.initials: G
authors.lastname: Assenza
authors.affiliation: Clinical Neurology, Campus Biomedico University of Rome, Rome, Italy.
authors.forename: Antonella
authors.initials: A
authors.lastname: Benvenga
authors.affiliation: Genetic Laboratory, E.O. Ospedali Galliera, Genova, Italy.
authors.forename: Elena
authors.initials: E
authors.lastname: Gennaro
authors.affiliation: Clinical Neurology, Campus Biomedico University of Rome, Rome, Italy.
authors.forename: Mario
authors.initials: M
authors.lastname: Tombini
authors.affiliation: Clinical Neurology, Campus Biomedico University of Rome, Rome, Italy.
authors.forename: Chiara
authors.initials: C
authors.lastname: Campana
authors.affiliation: Clinical Neurology, Campus Biomedico University of Rome, Rome, Italy.
authors.forename: Federica
authors.initials: F
authors.lastname: Assenza
authors.affiliation: Clinical Neurology, Campus Biomedico University of Rome, Rome, Italy.
authors.forename: Giovanni
authors.initials: G
authors.lastname: Di Pino
authors.affiliation: Clinical Neurology, Campus Biomedico University of Rome, Rome, Italy.
authors.forename: Vincenzo
authors.initials: V
authors.lastname: Di Lazzaro
mesh_terms: D002891:Chromosomes, Human, Pair 21 / Q000235:genetics; D055313:Cystatin B / Q000235:genetics*; D004252:DNA Mutational Analysis; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D010641:Phenotype; D017384:Sequence Deletion / Q000235:genetics*; D035781:Siblings; D020194:Unverricht-Lundborg Syndrome / Q000235:genetics*
chemical_list: D055313:Cystatin B
keywords: Gender; Heterozygous compound progressive myoclonic epilepsy; Progressive myoclonic epilepsy; Unverricht-Lundborg disease