C. Gómez-Abad, BSc,
P. Gómez-Garre, PhD,
E. Gutiérrez-Delicado, MD,
S. Saygi, MD,
R. Michelucci, MD,
C. A. Tassinari, MD,
S. Rodríguez de Córdoba, PhD and
J. M. Serratosa, MD, PhD
From the Neurology Service (Drs. Serratosa, Gómez-Garre, and Gutiérrez-Delicado, C. Gómez-Abad), Fundación Jiménez Díaz, Madrid, Spain; Hacettepe University Hospital (Dr. Saygi), Ankara, Turkey; Unità Operativa di Neurologia (Drs. Michelucci and Tassinari), Ospedale Bellaria C.A. Pizzardi, Bologna, Italy; and Departamento de Inmunología (Dr. Rodríguez de Córdoba), Centro de Investigaciones Biológicas, CSIC, Madrid, Spain.
Address correspondence and reprint requests to Dr. José Serratosa, Servicio de Neurología, Fundación Jiménez Díaz, Avda Reyes Católicos 2, 28040, Madrid, Spain; e-mail: serratosa{at}telefonica.net
Objective: To study EPM2B gene mutations and genotype-phenotypecorrelations in patients with Lafora disease.
Methods: The authors performed a clinical and mutational analysisof 25 patients, from 23 families, diagnosed with Lafora diseasewho had not shown mutations in the EPM2A gene.
Results: The authors identified 18 mutations in EPM2B, including12 novel mutations: 4 nonsense mutations (R265X, C26X, W219X,and E67X), a 6-base pair (bp) microdeletion resulting in a twoamino acid deletion (V294_K295del), a 4-bp insertion resultingin a frameshift mutation (S339fs12), and 6 missense mutations(D308A, I198N, C68Y, E67Q, P264H, and D233A). In our data setof 77 families with Lafora disease, 54 (70.1%) tested probandshave mutations in EPM2A, 21 (27.3%) in EPM2B, and 2 (2.6%) haveno mutations in either gene. The course of the disease was longerin patients with EPM2B mutations vs patients with EPM2A mutations.
Conclusions: Genetic allelic heterogeneity is present in Laforadisease associated with mutations in EPM2B. Patients with mutationsin EPM2A and EPM2B express similar clinical manifestation, althoughpatients with EPM2B-associated Lafora disease seem to have aslightly milder clinical course. The lack of mutations in EPM2Aand EPM2B in two families could be because of the presence ofmutations in noncoding, nontested regions or the existence ofan additional gene associated with Lafora disease.
Supported by the Asociación Lafora España, theFondo de Investigaciones Sanitarias (FIS PI020536, FIS 603/054),and Comisión Interministerial de Ciencia y Tecnología(SAF 99–0013-CO2–02). This study is based on worksupported by the Fundación Conchita Rábago deJiménez Díaz under fellowships awarded to C.G-A.
Received August 30, 2004. Accepted in final form November 22,2004.
This article has been cited by other articles:
M. C. Solaz-Fuster, J. V. Gimeno-Alcaniz, S. Ros, M. E. Fernandez-Sanchez, B. Garcia-Fojeda, O. C. Garcia, D. Vilchez, J. Dominguez, M. Garcia-Rocha, M. Sanchez-Piris, et al. Regulation of glycogen synthesis by the laforin-malin complex is modulated by the AMP-activated protein kinase pathway
Hum. Mol. Genet.,
March 1, 2008;
17(5):
667 - 678.
[Abstract][Full Text][PDF]
C. A. Worby, M. S. Gentry, and J. E. Dixon Malin Decreases Glycogen Accumulation by Promoting the Degradation of Protein Targeting to Glycogen (PTG)
J. Biol. Chem.,
February 15, 2008;
283(7):
4069 - 4076.
[Abstract][Full Text][PDF]
J. Turnbull, S. Kumar, Z.-P. Ren, S. Muralitharan, T. Naranian, C. A. Ackerley, and B. A. Minassian Lafora Progressive Myoclonus Epilepsy: Disease Course Homogeneity in a Genetic Isolate
J Child Neurol,
February 1, 2008;
23(2):
240 - 242.
[Abstract][PDF]
P. Gomez-Garre, E. Gutierrez-Delicado, C. Gomez-Abad, J. Morales-Corraliza, V. E. Villanueva, S. Rodriguez de Cordoba, J. Larrauri, M. Gutierrez, J. Berciano, and J. M. Serratosa Hepatic disease as the first manifestation of progressive myoclonus epilepsy of Lafora
Neurology,
April 24, 2007;
68(17):
1369 - 1373.
[Abstract][Full Text][PDF]
H. Lohi, J. Turnbull, X. C. Zhao, S. Pullenayegum, L. Ianzano, M. Yahyaoui, M. A. Mikati, N. P. Quinn, S. Franceschetti, F. Zara, et al. Genetic diagnosis in Lafora disease: Genotype-phenotype correlations and diagnostic pitfalls
Neurology,
March 27, 2007;
68(13):
996 - 1001.
[Abstract][Full Text][PDF]
S Singh, I Sethi, S Francheschetti, C Riggio, G Avanzini, K Yamakawa, A V Delgado-Escueta, and S Ganesh Novel NHLRC1 mutations and genotype-phenotype correlations in patients with Lafora's progressive myoclonic epilepsy.
J. Med. Genet.,
September 1, 2006;
43(9):
e48 - e48.
[Abstract][Full Text][PDF]
