Franceschetti Silvana, Gambardella Antonio, Canafoglia Laura, Striano Pasquale, Lohi Hannes, Gennaro Elena, Ianzano Leonarda, Veggiotti Pierangelo, Sofia Vito, Biondi Roberto, Striano Salvatore, Gellera Cinzia, Annesi Grazia, Madia Francesca, Civitelli Donata, Rocca Francesca E, Quattrone Aldo, Avanzini Giuliano, Minassian Berge, Zara Federico
Department of Clinical Neurophysiology, Istituto Nazionale Neurologico C. Besta, Milan, Italy.
Epilepsia. 2006 Mar;47(3):640-3. doi: 10.1111/j.1528-1167.2006.00479.x.
EPM2B mutations have been found in a variable proportion of patients with Lafora disease (LD). Genotype-phenotype correlations suggested that EPM2B patients show a slower course of the disease, with delayed age at death, compared with EPM2A patients. We herein report clinical and genetic findings of 26 Italian LD patients.
Disease progression was evaluated by means of a disability scale based on residual motor and cognitive functions and daily living and social abilities, at 4 years from the onset. Mutational analysis was performed by sequencing the coding regions of the EPM2A and EPM2B genes.
Age at onset ranged from 8.5 to 18.5 years (mean, 13.7+/-2.6). The mean duration of follow-up was 7.1+/-3.9 years. Daily living activities and social interactions were preserved in five of 24 patients. The remaining patients showed moderate to extremely severe limitations of daily living and social abilities. Sixteen (72%) of 22 families showed mutations in the EPM2B gene, and five (22%), in the EPM2A gene. One family showed no mutations. A novel EPM2B mutation also was identified.
In our series, EPM2B mutations occurred in 72% of families, thus indicating that EPM2B is the major gene for LD in the Italian population. Moreover, we found that six of 17 EPM2B patients preserved daily living activities and social interactions at 4 years from onset, suggesting a slow disease progression. Additional clinical and functional studies will clarify whether specific mutations may influence the course of the disease in LD patients.
在不同比例的拉福拉病（LD）患者中发现了EPM2B基因突变。基因型-表型相关性研究表明，与EPM2A患者相比，EPM2B患者的疾病进展较慢，死亡年龄延迟。我们在此报告26例意大利LD患者的临床和基因研究结果。
在发病4年后，通过基于残余运动和认知功能以及日常生活和社交能力的残疾量表评估疾病进展。通过对EPM2A和EPM2B基因的编码区进行测序来进行突变分析。
发病年龄范围为8.5至18.5岁（平均13.7±2.6岁）。平均随访时间为7.1±3.9年。24例患者中有5例的日常生活活动和社交互动得以保留。其余患者表现出中度至极重度的日常生活和社交能力受限。22个家族中有16个（72%）显示EPM2B基因突变，5个（22%）显示EPM2A基因突变。1个家族未发现突变。还鉴定出一种新的EPM2B突变。
在我们的研究系列中，72%的家族发生了EPM2B基因突变，这表明EPM2B是意大利人群中LD的主要基因。此外，我们发现17例EPM2B患者中有6例在发病4年后仍保留日常生活活动和社交互动，提示疾病进展缓慢。更多的临床和功能研究将阐明特定突变是否可能影响LD患者的疾病进程。
