背景:Lafora病(LD)是一种严重的进行性肌阵挛性癫痫,其特征是全身性癫痫发作,肌阵鸣,智力下降,共济失调,痉挛,构音障碍,视觉损失,在后期阶段,精神病和痴呆症。迄今为止,EPM2A和EPM2B/NHLRC1基因的突变已被确定为LD的常见原因。然而,在一个患有早发性拉福拉病的巴基斯坦家庭中,仅报道了一次PRDM8突变.在本研究中,我们报告了具有PRDM8突变的第二个家族。
方法:最初被诊断为复杂性遗传性痉挛性截瘫(HSP)的伊朗家庭的两名受影响个体接受了仔细的神经系统检查。进行纯合性作图和全外显子组测序。根据检测拉福拉尸体的遗传分析结果,做了皮肤活检.
结果:描述了患者的临床特征。鉴定了与4号染色体的连锁和PRDM8基因的突变,提示患者可能受到早发性LD的影响。然而,就像巴基斯坦家庭一样,在他们的皮肤活检中寻找Lafora尸体是阴性的。他们的脑电图显示,在没有临床癫痫发作的情况下,全身性癫痫样放电。
结论:本研究增加了PRDM8相关病例的数量,并扩大了PRDM8基因突变的表型谱。两个报告的PRDM8相关家庭都表现出家族内和家族间的异质性,它们起源于中东。因此,似乎PRDM8突变不仅在LD中,而且在其他神经退行性疾病中,如复杂的HSP样表型,尤其是在这个地区。
BACKGROUND: Lafora disease (LD) is a severe form of progressive myoclonus epilepsy characterized by generalized seizures, myoclonus, intellectual decline, ataxia, spasticity, dysarthria, visual loss, and in later stages, psychosis and dementia. To date, mutations in the EPM2A and EPM2B/NHLRC1 genes have been identified as the common causes of LD. However, a mutation in PRDM8 has been reported only once in a Pakistani family affected with early-onset Lafora disease. In the present study, we report the second family with a PRDM8 mutation.
METHODS: Two affected individuals of an Iranian family initially diagnosed as complicated hereditary spastic paraplegia (HSP) underwent careful neurologic examination. Homozygosity mapping and whole-exome sequencing were performed. Based on the results of genetic analysis to detection of Lafora bodies, a skin biopsy was done.
RESULTS: The clinical features of the patients were described. Linkage to chromosome 4 and a mutation in the PRDM8 gene were identified, suggesting the patients may be affected with early-onset LD. However, like the Pakistani family, the search for Lafora bodies in their skin biopsies was negative. Their electroencephalograms showed generalized epileptiform discharges in the absence of clinical seizures.
CONCLUSIONS: The current study increases the number of PRDM8-related cases and expands the phenotypic spectrum of mutations in the PRDM8 gene. Both reported PRDM8-related families presented intra and inter-familial heterogeneity and they have originated from the Middle East. Thus, it seems the PRDM8 mutations should be considered not only in LD but also in other neurodegenerative disorders such as a complicated HSP-like phenotype, especially in this region.