Mutations in the Gene Encoding Cystatin B in Progressive Myoclonus Epilepsy (EPM1)

• Published in: Science (American Association for the Advancement of Science) Vol. 271; no. 5256; pp. 1731 - 1734
• Main Authors: Pennacchio, Len A., Lehesjoki, Anna-Elina, Stone, Nancy E., Willour, Virginia L., Virtaneva, Kimmo, Miao, Jinmin, D'Amato, Elena, Ramirez, Lucia, Faham, Malek, Koskiniemi, Marjaleena, Warrington, Janet A., Norio, Reijo, de la Chapelle, Albert, Cox, David R., Myers, Richard M.
• Format: Journal Article
• Language: English
• Published: Washington, DC American Society for the Advancement of Science 22.03.1996; American Association for the Advancement of Science; The American Association for the Advancement of Science
• Subjects: Alleles; Amino Acid Sequence; Animal mutation; Base Sequence; Biological and medical sciences; Chromosome Mapping; Chromosomes; Chromosomes, Human, Pair 21 - genetics; Coding; Codon, Terminator - genetics; Complementary DNA; Cystatin B; Cystatins; Cystatins - chemistry; Cystatins - genetics; Cysteine Proteinase Inhibitors - chemistry; Cysteine Proteinase Inhibitors - genetics; DNA; Epilepsies, Myoclonic - genetics; Epilepsy; Etiology; Family (Sociological Unit); Female; Finland; Gene Expression; Genes; Genes, Recessive; Genetic aspects; Genetic mutation; Genetics; Headache. Facial pains. Syncopes. Epilepsia. Intracranial hypertension. Brain oedema. Cerebral palsy; Humans; Introns - genetics; Linkage Disequilibrium; Male; Medical sciences; Messenger RNA; Molecular Sequence Data; Mutation; Myoclonus; Nervous system (semeiology, syndromes); Neurology; Patients; Pedigree; Point Mutation; Polymerase Chain Reaction; Recombination, Genetic; RNA, Messenger - genetics; RNA, Messenger - metabolism; Seizures; Finland; Human; Cystatin; Nervous system diseases; Chromosome G21; Enzyme inhibitor; Progressive myoclonus epilepsy; Gene expression; Cerebral disorder; Genetic disease; Gene; Central nervous system disease; Genetics; Degenerative disease; Mutation
• ISSN: 0036-8075; 1095-9203
• DOI: 10.1126/science.271.5256.1731

Progressive myoclonus epilepsy of the Unverricht-Lundborg type (EPM1) is an autosomal recessive inherited form of epilepsy, previously linked to human chromosome 21q22.3. The gene encoding cystatin B was shown to be localized to this region, and levels of messenger RNA encoded by this gene were found to be decreased in cells from affected individuals. Two mutations, a 3′ splice site mutation and a stop codon mutation, were identified in the gene encoding cystatin B in EPM1 patients but were not present in unaffected individuals. These results provide evidence that mutations in the gene encoding cystatin B are responsible for the primary defect in patients with EPM1.