RESUMEN
BACKGROUND: Juvenile myoclonic epilepsy (JME) accounts for 3 to 12% of all epilepsies. In 2004, the GENESS Consortium demonstrated four missense mutations in Myoclonin1/EFHC1 of chromosome 6p12.1 segregating in 20% of Hispanic families with JME. OBJECTIVE: To examine what percentage of consecutive JME clinic cases have mutations in Myoclonin1/EFHC1. METHODS: We screened 44 consecutive patients from Mexico and Honduras and 67 patients from Japan using heteroduplex analysis and direct sequencing. RESULTS: We found five novel mutations in transcripts A and B of Myoclonin1/EFHC1. Two novel heterozygous missense mutations (c.755C>A and c.1523C>G) in transcript A occurred in both a singleton from Mexico and another singleton from Japan. A deletion/frameshift (C.789del.AV264fsx280) in transcript B was present in a mother and daughter from Mexico. A nonsense mutation (c.829C>T) in transcript B segregated in four clinically and seven epileptiform-EEG affected members of a large Honduran family. The same nonsense mutation (c.829C>T) occurred as a de novo mutation in a sporadic case. Finally, we found a three-base deletion (-364--362del.GAT) in the promoter region in a family from Japan. CONCLUSION: Nine percent of consecutive juvenile myoclonic epilepsy cases from Mexico and Honduras clinics and 3% of clinic patients from Japan carry mutations in Myoclonin1/EFCH1. These results represent the highest number and percentage of mutations found for a juvenile myoclonic epilepsy causing gene of any population group.
Asunto(s)
Proteínas de Unión al Calcio/genética , Salud de la Familia , Mutación , Epilepsia Mioclónica Juvenil/genética , Canales de Cloruro CLC-2 , Canales de Cloruro/genética , Análisis Mutacional de ADN/métodos , Femenino , Genotipo , Honduras/epidemiología , Humanos , Japón , Masculino , México/epidemiología , Epilepsia Mioclónica Juvenil/epidemiología , Fenotipo , Regiones Promotoras Genéticas , Receptores de GABA-A/genéticaAsunto(s)
Salud de la Familia , Epilepsia Mioclónica Juvenil/genética , Adolescente , Adulto , Edad de Inicio , Mapeo Cromosómico/métodos , Demografía , Electroencefalografía/métodos , Epilepsia/complicaciones , Epilepsia Tipo Ausencia/complicaciones , Epilepsia Tipo Ausencia/genética , Femenino , Humanos , Masculino , Persona de Mediana Edad , Epilepsia Mioclónica Juvenil/clasificación , Epilepsia Mioclónica Juvenil/etiología , Fenotipo , Riesgo , Factores SexualesRESUMEN
Amongst idiopathic generalized epilepsies, juvenile myoclonic epilepsy (JME) is the most common, accounting for 12% to 30% of all epilepsies in the Western world. Classic JME consists of awakening myoclonias, grand mal convulsions and EEG 4 to 6 Hz polyspike waves that appear in adolescence. Probands and affected family members do not have pyknoleptic 3Hz spike and wave absences. However, in 10 to 30% of patients, rare or spanioleptic polyspike wave absences appear. In 1988,1995,1996,we mapped classic JME to a 7 cM locus in chromosome 6p12 11, called EJM1, using families from Los Angeles and Belize. In 2001,we studied one large family from Belize and 21 new families from Los Angeles and Mexico Cities, aided by a BAC/PAC based physical map and 6 new dinucleotide repeats, to narrow EJM1 to an interval between D6S272 and D6S1573. In 2002, we found myoclonin, the putative gene for typical JME in 6p12. At the congress, we will reveal the identity of the myoclonin gene, its putative function and discuss the significance of this discovery in the JME population at large.