Ahmad Arsalan, Dad Rubina, Ullah Muhammad Ikram, Baig Tahir Ahmed, Ahmad Imran N, Nasir Abdul, Hübner Christian A, Hassan Muhammad Jawad
Division of Neurology, Shifa International Hospital, Shifa Tameer e Millat University, Islamabad, Pakistan.
Department of Healthcare Biotechnology, Atta-ur-Rahman School of Applied Biosciences (ASAB), National University of Sciences & Technology (NUST), Islamabad, Pakistan.
J Neurol Sci. 2017 Feb 15;373:263-267. doi: 10.1016/j.jns.2017.01.010. Epub 2017 Jan 4.
Lafora disease (LD) is progressive myoclonic epilepsy with late childhood- to teenage-onset. Mutations in two genes, EPM2A and NHLRC1, are responsible for this autosomal recessive disease in many patients Worldwide. In present study, we reported two unrelated consanguineous Pakistani families with Lafora disease (Families A and B). Affected individuals in both families presented with generalized tonic clonic seizures, intellectual disability, ataxia and cognitive decline. Diagnosis of Lafora disease was made on histo-pathological analysis of the skin biopsy, found positive for lafora bodies in periodic acid schiff stain and frequent generalized epileptiform discharges on electroencephalogram (EEG). Bi-directional sequencing in family A was performed for EPM2A and NHLRC1 genes but no mutation was found. In family B, Illumina TruSight One Sequencing Panel covering 4813 OMIM genes was carried out and we identified a novel homozygous mutation c.95G>T; p.32Trp>Leu of EPM2A gene which was found co-segregated in this family through Sanger sequencing. Structural analysis of this mutation, through different in silico approaches, predicted loss of stability and conformation in Laforin protein.
拉福拉病（LD）是一种迟发性儿童至青少年期起病的进行性肌阵挛癫痫。在全球许多患者中，EPM2A和NHLRC1这两个基因的突变是导致这种常染色体隐性疾病的原因。在本研究中，我们报告了两个患有拉福拉病的不相关近亲巴基斯坦家庭（A家庭和B家庭）。两个家庭中的患病个体均出现全身性强直阵挛发作、智力残疾、共济失调和认知衰退。通过对皮肤活检进行组织病理学分析确诊为拉福拉病，在高碘酸希夫染色中发现拉福拉小体呈阳性，脑电图（EEG）显示频繁出现全身性癫痫样放电。对A家庭的EPM2A和NHLRC1基因进行了双向测序，但未发现突变。在B家庭中，使用覆盖4813个《在线人类孟德尔遗传》（OMIM）基因的Illumina TruSight One测序板进行检测，我们鉴定出EPM2A基因一个新的纯合突变c.95G>T；p.32Trp>Leu，通过桑格测序发现该突变在这个家庭中呈共分离现象。通过不同的计算机模拟方法对该突变进行结构分析，预测拉福林蛋白的稳定性和构象丧失。
