Clinical and genetic findings in 26 Italian patients with Lafora disease
Clinical and genetic findings in 26 Italian patients with Lafora disease
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DOI：
10.1111/j.1528-1167.2006.00479.x
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发表时间：
2006-03-01
期刊：
影响因子：
5.6
通讯作者：
Zara, F
中科院分区：
文献类型：
--
作者：
Franceschetti, S;Gambardella, A;Zara, F
目的：在不同比例的Lafora病（LD）患者中发现了EPM 2B突变。基因型-表型相关性表明，与EPM 2A患者相比，EPM 2B患者的病程较慢，死亡年龄延迟。我们在此报告26意大利LD patients.Methods：疾病进展的临床和遗传学研究结果进行了评估，通过残疾量表的基础上残留的运动和认知功能，日常生活和社会能力，在4年的发病。突变分析进行测序的编码区的EPM 2A和EPM 2B基因。结果：发病年龄范围为8.5至18.5岁（平均值，13.7 +/- 2.6）。平均随访时间为7.1 ± 3.9年。24例患者中有5例保留了日常生活活动和社会交往。其余患者表现出中度至极重度的日常生活和社交能力限制。22个家系中有16个（72%）在EPM 2B基因上有突变，5个（22%）在EPM 2A基因上有突变。一个家庭没有表现出突变。一个新的EPM 2B突变也被identified.Conclusions：在我们的系列，EPM 2B突变发生在72%的家庭，从而表明EPM 2B是主要的基因LD在意大利人口。此外，我们发现17例EPM 2B患者中有6例在发病后4年内保留了日常生活活动和社会交往，表明疾病进展缓慢。其他临床和功能研究将阐明特定突变是否可能影响LD患者的病程。
Purpose: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.Methods: 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.Results: 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.Conclusions: 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.