Note to users. If you're seeing this message, it means that your browser cannot find this page's style/presentation instructions -- or possibly that you are using a browser that does not support current Web standards. Find out more about why this message is appearing, and what you can do to make your experience of our site the best it can be.

Science 22 March 1996:
Vol. 271. no. 5256, pp. 1731 - 1734
DOI: 10.1126/science.271.5256.1731
Prev | Table of Contents | Next

Reports

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

Len A. Pennacchio, Anna-Elina Lehesjoki, Nancy E. Stone, Virginia L. Willour, Kimmo Virtaneva, Jinmin Miao, Elena D'Amato, Lucia Ramirez, Malek Faham, Marjaleena Koskiniemi, Janet A. Warrington, Reijo Norio, Albert de la Chapelle, David R. Cox, Richard M. Myers *

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.

L. A. Pennacchio, Department of Genetics, Stanford University School of Medicine, and Department of Biology, Stanford University, Stanford, CA 94305, USA.
A.-E. Lehesjoki, K. Virtaneva, J. Miao, E. D'Amato, A. de la Chapelle, Department of Medical Genetics, University of Helsinki, Haartmaninkatu 3, 00290 Helsinki, Finland.
N. E. Stone, V. L. Willour, L. Ramirez, M. Faham, J. A. Warrington, D. R. Cox, R. M. Myers, Department of Genetics, Stanford University School of Medicine, Stanford, CA 94305, USA.
M. Koskiniemi, Department of Virology, University of Helsinki, Haartmaninkatu 3, 00290 Helsinki, Finland.
R. Norio, Department of Medical Genetics, Finnish Population and Family Welfare Federation, 00100 Helsinki, Finland.
* To whom correspondence should be addressed.


THIS ARTICLE HAS BEEN CITED BY OTHER ARTICLES:
Motor cortex and thalamic atrophy in Unverricht-Lundborg disease: Voxel-based morphometric study.
P. Koskenkorva, J. Khyuppenen, E. Niskanen, M. Kononen, P. Bendel, E. Mervaala, A. E. Lehesjoki, R. Kalviainen, and R. Vanninen (2009)
Neurology 73, 606-611
   Abstract »    Full Text »    PDF »
Cystatin B Deficiency Sensitizes Neurons to Oxidative Stress in Progressive Myoclonus Epilepsy, EPM1.
M. K. Lehtinen, S. Tegelberg, H. Schipper, H. Su, H. Zukor, O. Manninen, O. Kopra, T. Joensuu, P. Hakala, A. Bonni, et al. (2009)
J. Neurosci. 29, 5910-5915
   Abstract »    Full Text »    PDF »
Identification of Cystatin B as a Potential Serum Marker in Hepatocellular Carcinoma.
M.-J. Lee, G.-R. Yu, S.-H. Park, B.-H. Cho, J.-S. Ahn, H.-J. Park, E.-Y. Song, and D.-G. Kim (2008)
Clin. Cancer Res. 14, 1080-1089
   Abstract »    Full Text »    PDF »
Hyperostosis frontalis interna as a novel finding in Unverricht-Lundborg disease.
M. Korja, V. Kaasinen, S. Lamusuo, R. J. Marttila, and R. Parkkola (2007)
Neurology 68, 1077-1078
   Full Text »    PDF »
Cystatin M/E Is a High Affinity Inhibitor of Cathepsin V and Cathepsin L by a Reactive Site That Is Distinct from the Legumain-binding Site: A NOVEL CLUE FOR THE ROLE OF CYSTATIN M/E IN EPIDERMAL CORNIFICATION.
T. Cheng, K. Hitomi, I. M. J. J. van Vlijmen-Willems, G. J. de Jongh, K. Yamamoto, K. Nishi, C. Watts, T. Reinheckel, J. Schalkwijk, and P. L. J. M. Zeeuwen (2006)
J. Biol. Chem. 281, 15893-15899
   Abstract »    Full Text »    PDF »
Frataxin deficiency alters heme pathway transcripts and decreases mitochondrial heme metabolites in mammalian cells.
R. A. Schoenfeld, E. Napoli, A. Wong, S. Zhan, L. Reutenauer, D. Morin, A. R. Buckpitt, F. Taroni, B. Lonnerdal, M. Ristow, et al. (2005)
Hum. Mol. Genet. 14, 3787-3799
   Abstract »    Full Text »    PDF »
The genetic and molecular bases of monogenic disorders affecting proteolytic systems.
I Richard (2005)
J. Med. Genet. 42, 529-539
   Abstract »    Full Text »    PDF »
Normal Sexual Development and Fertility in testatin Knockout Mice.
V. Tohonen, J. Frygelius, M. Mohammadieh, U. Kvist, L. J. Pelliniemi, K. O'Brien, K. Nordqvist, and A. Wedell (2005)
Mol. Cell. Biol. 25, 4892-4902
   Abstract »    Full Text »    PDF »
A new clinical and molecular form of Unverricht-Lundborg disease localized by homozygosity mapping.
S. F. Berkovic, A. Mazarib, S. Walid, M. Y. Neufeld, J. Manelis, Y. Nevo, A. D. Korczyn, J. Yin, L. Xiong, M. Pandolfo, et al. (2005)
Brain 128, 652-658
   Abstract »    Full Text »    PDF »
A new locus for a childhood onset, slowly progressive autosomal recessive spinocerebellar ataxia maps to chromosome 11p15.
G J Breedveld, B van Wetten, G D te Raa, E Brusse, J C van Swieten, B A Oostra, and J A Maat-Kievit (2004)
J. Med. Genet. 41, 858-866
   Full Text »    PDF »
The loss of circadian PAR bZip transcription factors results in epilepsy.
F. Gachon, P. Fonjallaz, F. Damiola, P. Gos, T. Kodama, J. Zakany, D. Duboule, B. Petit, M. Tafti, and U. Schibler (2004)
Genes & Dev. 18, 1397-1412
   Abstract »    Full Text »    PDF »
Evidence that unrestricted legumain activity is involved in disturbed epidermal cornification in cystatin M/E deficient mice.
P. L.J.M. Zeeuwen, I. M.J.J. van Vlijmen-Willems, D. Olthuis, H. T. Johansen, K. Hitomi, I. Hara-Nishimura, J. C. Powers, K. E. James, H. J. op den Camp, R. Lemmens, et al. (2004)
Hum. Mol. Genet. 13, 1069-1079
   Abstract »    Full Text »    PDF »
Cystatin 10, a Novel Chondrocyte-specific Protein, May Promote the Last Steps of the Chondrocyte Differentiation Pathway.
Y. Koshizuka, T. Yamada, K. Hoshi, T. Ogasawara, U.-i. Chung, H. Kawano, Y. Nakamura, K. Nakamura, S. Ikegawa, and H. Kawaguchi (2003)
J. Biol. Chem. 278, 48259-48266
   Abstract »    Full Text »    PDF »
Cystatin E1 and E2, New Members of Male Reproductive Tract Subgroup Within Cystatin Type 2 Family.
Y. Li, P. J. Friel, D. J. McLean, and M. D. Griswold (2003)
Biol Reprod 69, 489-500
   Abstract »    Full Text »    PDF »
Efficacy of levetiracetam in a patient with Unverricht-Lundborg progressive myoclonic epilepsy.
P. Kinrions, N. Ibrahim, K. Murphy, A.-E. Lehesjoki, I. Jarvela, and N. Delanty (2003)
Neurology 60, 1394-1395
   Full Text »    PDF »
The Cystatin-Related Epididymal Spermatogenic Protein Inhibits the Serine Protease Prohormone Convertase 2.
G. A. Cornwall, A. Cameron, I. Lindberg, D. M. Hardy, N. Cormier, and N. Hsia (2003)
Endocrinology 144, 901-908
   Abstract »    Full Text »    PDF »
Cres2 and Cres3: New Members of the Cystatin-Related Epididymal Spermatogenic Subgroup of Family 2 Cystatins.
N. Hsia and G. A. Cornwall (2003)
Endocrinology 144, 909-915
   Abstract »    Full Text »    PDF »
Identification of a Monogenic Locus (jams1) Causing Juvenile Audiogenic Seizures in Mice.
H. Misawa, E. H. Sherr, D. J. Lee, D. M. Chetkovich, A. Tan, C. E. Schreiner, and D. S. Bredt (2002)
J. Neurosci. 22, 10088-10093
   Abstract »    Full Text »    PDF »
A null mutation in the cystatin M/E gene of ichq mice causes juvenile lethality and defects in epidermal cornification.
P. L.J.M. Zeeuwen, I. M.J.J. van Vlijmen-Willems, W. Hendriks, G. F.M. Merkx, and J. Schalkwijk (2002)
Hum. Mol. Genet. 11, 2867-2875
   Abstract »    Full Text »    PDF »
New insights into the molecular basis of progressive myoclonus epilepsy: a multiprotein complex with cystatin B.
R. Di Giaimo, M. Riccio, S. Santi, C. Galeotti, D. C. Ambrosetti, and M. Melli (2002)
Hum. Mol. Genet. 11, 2941-2950
   Abstract »    Full Text »    PDF »
Brainstem involvement in Unverricht-Lundborg disease (EPM1): An MRI and 1H MRS study.
M. Mascalchi, R. Michelucci, M. Cosottini, C. Tessa, F. Lolli, P. Riguzzi, A. E. Lehesjoki, M. Tosetti, N. Villari, and C. A. Tassinari (2002)
Neurology 58, 1686-1689
   Abstract »    Full Text »    PDF »
Isolation of the human testatin gene and analysis in patients with abnormal gonadal development.
A. Eriksson, V. Tohonen, A. Wedell, and K. Nordqvist (2002)
Mol. Hum. Reprod. 8, 8-15
   Abstract »    Full Text »    PDF »
Disruption of PPT1 or PPT2 causes neuronal ceroid lipofuscinosis in knockout mice.
P. Gupta, A. A. Soyombo, A. Atashband, K. E. Wisniewski, J. M. Shelton, J. A. Richardson, R. E. Hammer, and S. L. Hofmann (2001)
PNAS 98, 13566-13571
   Abstract »    Full Text »    PDF »
Unverricht-Lundborg disease in a five-generation Arab family: Instability of dodecamer repeats.
A. Mazarib, L. Xiong, M.Y. Neufeld, M. Birnbaum, A.D. Korczyn, M. Pandolfo, and S.F. Berkovic (2001)
Neurology 57, 1050-1054
   Abstract »    Full Text »    PDF »
Cystatin B-deficient mice have increased expression of apoptosis and glial activation genes.
K. Lieuallen, L. A. Pennacchio, M. Park, R. M. Myers, and G. G. Lennon (2001)
Hum. Mol. Genet. 10, 1867-1871
   Abstract »    Full Text »    PDF »
A Patient With 2 Different Repeat Expansion Mutations.
P. Nokelainen, H. Heiskala, A.-E. Lehesjoki, and M. Kaski (2000)
Arch Neurol 57, 1199-1203
   Abstract »    Full Text »    PDF »
Current topic: Genetics of childhood epilepsy.
R. Robinson and M. Gardiner (2000)
Arch. Dis. Child. 82, 121-125
   Full Text »
Perfect Conserved Linkage Across the Entire Mouse Chromosome 10 Region Homologous to Human Chromosome 21.
T. Wiltshire, M. Pletcher, S. E. Cole, M. Villanueva, B. Birren, J. Lehoczky, K. Dewar, and R. H. Reeves (1999)
Genome Res. 9, 1214-1222
   Abstract »    Full Text »
Genetic localization of the familial adult myoclonic epilepsy (FAME) gene to chromosome 8q24.
N. M. Plaster, E. Uyama, M. Uchino, T. Ikeda, K. M. Flanigan, I. Kondo, and L. J. Ptacek (1999)
Neurology 53, 1180
   Abstract »    Full Text »    PDF »
Altered spacing of promoter elements due to the dodecamer repeat expansion contributes to reduced expression of the cystatin B gene in EPM1.
M. D. Lalioti, H. S. Scott, and S. E. Antonarakis (1999)
Hum. Mol. Genet. 8, 1791-1798
   Abstract »    Full Text »    PDF »
Molecular genetics of the Finnishdisease heritage.
L. Peltonen, A. Jalanko, and T. Varilo (1999)
Hum. Mol. Genet. 8, 1913-1923
   Abstract »    Full Text »    PDF »
Mapping Loci for Pentylenetetrazol-Induced Seizure Susceptibility in Mice.
T. N. Ferraro, G. T. Golden, G. G. Smith, P. St. Jean, N. J. Schork, N. Mulholland, C. Ballas, J. Schill, R. J. Buono, and W. H. Berrettini (1999)
J. Neurosci. 19, 6733-6739
   Abstract »    Full Text »    PDF »
Cystatin-Related Epididymal Spermatogenic Protein Colocalizes with Luteinizing Hormone-{beta} Protein in Mouse Anterior Pituitary Gonadotropes.
H. G. Sutton, A. Fusco, and G. A. Cornwall (1999)
Endocrinology 140, 2721-2732
   Abstract »    Full Text »
{blacksquare} REVIEW : Long-Term Modulation of Gene Expression in Epilepsy.
R. J. Delorenzo and T. A. Morris (1999)
Neuroscientist 5, 86-99
   Abstract »    PDF »
Linkage disequilibrium mapping in isolated populations: The example of Finland revisited.
A. de la Chapelle and F. A. Wright (1998)
PNAS 95, 12416-12423
   Abstract »    Full Text »    PDF »
Cystatin F Is a Glycosylated Human Low Molecular Weight Cysteine Proteinase Inhibitor.
J. Ni, M. A. Fernandez, L. Danielsson, R. A. Chillakuru, J. Zhang, A. Grubb, J. Su, R. Gentz, and M. Abrahamson (1998)
J. Biol. Chem. 273, 24797-24804
   Abstract »    Full Text »    PDF »
Structure and Transcriptional Regulation of the Human Cystatin A Gene. THE 12-O-TETRADECANOYLPHORBOL-13-ACETATE (TPA) RESPONSIVE ELEMENT-2 SITE (-272 TO -278) ON CYSTATIN A GENE IS CRITICAL FOR TPA-DEPENDENT REGULATION.
H. Takahashi, K. Asano, M. Kinouchi, A. Ishida-Yamamoto, K. D. Wuepper, and H. Iizuka (1998)
J. Biol. Chem. 273, 17375-17380
   Abstract »    Full Text »    PDF »
Deficiency in Protein L-Isoaspartyl Methyltransferase Results in a Fatal Progressive Epilepsy.
A. Yamamoto, H. Takagi, D. Kitamura, H. Tatsuoka, H. Nakano, H. Kawano, H. Kuroyanagi, Y.-i. Yahagi, S.-i. Kobayashi, K.-i. Koizumi, et al. (1998)
J. Neurosci. 18, 2063-2074
   Abstract »    Full Text »    PDF »
Piracetam relieves symptoms in progressive myoclonus epilepsy: a multicentre, randomised, double blind, crossover study comparing the efficacy and safety of three dosages of oral piracetam with placebo.
M. Koskiniemi, B. Van Vleymen, L. Hakamies, S. Lamusuo, and J. Taalas (1998)
J. Neurol. Neurosurg. Psychiatry 64, 344-348
   Abstract »    Full Text »    PDF »
High-Resolution Mapping and Transcript Identification at the Progressive Epilepsy with Mental Retardation Locus on Chromosome 8p.
S. Ranta, A.-E. Lehesjoki, M. d. F. Bonaldo, J. A. Knowles, A. Hirvasniemi, B. Ross, P. J. de Jong, M. B. Soares, A. de la Chapelle, and T. C. Gilliam (1997)
Genome Res. 7, 887-896
   Abstract »    Full Text »    PDF »
Sensitivity to Jerky Gene Dosage Underlies Epileptic Seizures in Mice.
G. P. Donovan, C. Harden, J. Gal, L. Ho, E. Sibille, R. Trifiletti, L. J. Gudas, and M. Toth (1997)
J. Neurosci. 17, 4562-4569
   Abstract »    Full Text »    PDF »
Tissue Inhibitor of Metalloproteinases-1 (TIMP-1) Is Differentially Induced in Neurons and Astrocytes after Seizures: Evidence for Developmental, Immediate Early Gene, and Lesion Response.
S. Rivera, E. Tremblay, S. Timsit, O. Canals, Y. Ben-Ari, and M. Khrestchatisky (1997)
J. Neurosci. 17, 4223-4235
   Abstract »    Full Text »    PDF »
Isolation and genomic structure of a human homolog of the yeast periodic tryptophan protein 2 (PWP2) gene mapping to 21q22.3..
R G Lafreniere, D L Rochefort, N Chretien, C E Neville, R G Korneluk, L Zuo, Y Wei, J Lichter, and G A Rouleau (1996)
Genome Res. 6, 1216-1226
   Abstract »    PDF »
Isolation and characterization of the mouse cystatin B gene..
L A Pennacchio and R M Myers (1996)
Genome Res. 6, 1103-1109
   Abstract »    PDF »
Molecular and Cellular Plasticity in Developing Epileptic Brain.
J.L. Noebels, M.L. Sutherland, W.K. Nahm, and E. DiPasquale (1996)
Cold Spring Harb Symp Quant Biol 61, 319-326
   Abstract »    PDF »
Neuronal Sorting and Processing of Amyloid Precursor Protein: Implications for Alzheimer's Disease.
P.J. Tienari, B. De Strooper, E. Ikonen, N. Ida, M. Simons, C.L. Masters, C.G. Dotti, and K. Beyreuther (1996)
Cold Spring Harb Symp Quant Biol 61, 575-585
   Abstract »    PDF »
Extracellular Proteases in Neuronal Function and Degeneration.
S. Strickland, A. Gualandris, A.D. Rogove, and S.E. Tsirka (1996)
Cold Spring Harb Symp Quant Biol 61, 739-745
   Abstract »    PDF »
Lysosomal Protease Pathways to Apoptosis. CLEAVAGE OF Bid, NOT PRO-CASPASES, IS THE MOST LIKELY ROUTE.
V. Stoka, B. Turk, S. L. Schendel, T.-H. Kim, T. Cirman, S. J. Snipas, L. M. Ellerby, D. Bredesen, H. Freeze, M. Abrahamson, et al. (2001)
J. Biol. Chem. 276, 3149-3157
   Abstract »    Full Text »    PDF »


To Advertise     Find Products

Science. ISSN 0036-8075 (print), 1095-9203 (online)