Kecmanović M, Jović N, Keckarević-Marković M, Keckarević D, Stevanović G, Ignjatović P, Romac S
Center for Human Molecular Genetics, Faculty of Biology, University of Belgrade, Belgrade, Serbia.
Clinic of Neurology and Psychiatry for Children and Youth, School of Medicine, University of Belgrade, Belgrade, Serbia.
Clin Genet. 2016 Jan;89(1):104-8. doi: 10.1111/cge.12570. Epub 2015 Mar 19.
Lafora disease (LD) is an autosomal recessive, progressive disorder characterized by myoclonus and seizures, inexorable neurologic deterioration, cognitive decline and poor prognosis. LD is caused by mutations either in the EPM2A or in NHLRC1 genes. Here we report clinical and genetic findings on 14 LD patients from 10 families of Serbian/Montenegrin origin. Molecular diagnostics was performed by sequencing the coding regions of the EPM2A and NHLRC1 genes. In addition, haplotype analysis of the chromosomes carrying the two most frequent mutations (c.1048-1049delGA and deletion of the whole NHLRC1 gene) using eight different markers flanking the NHLRC1 gene was conducted. We identified one new mutation (c.1028T>C) along with the 3 previously reported mutations (c.1048-1049delGA, c.990delG, deletion of the whole NHLRC1 gene), all of which were located on the NHLRC1 gene. The two predominant mutations (c.1048-1049delGA and complete NHLRC1 gene deletion) appear to be founder mutations. In addition to documenting the genetic heterogeneity observed for LD, our study suggests that mutations in the NHLRC1 gene may be a common cause of LD in the Serbian/Montenegrin population, primarily because of a founder effect.
拉福拉病（LD）是一种常染色体隐性进行性疾病，其特征为肌阵挛和癫痫发作、不可阻挡的神经功能恶化、认知衰退以及预后不良。LD由EPM2A或NHLRC1基因突变引起。在此，我们报告了来自10个塞尔维亚/黑山裔家庭的14例LD患者的临床和基因研究结果。通过对EPM2A和NHLRC1基因的编码区进行测序来进行分子诊断。此外，使用位于NHLRC1基因两侧的8种不同标记，对携带两种最常见突变（c.1048 - 1049delGA和整个NHLRC1基因缺失）的染色体进行单倍型分析。我们鉴定出一个新突变（c.1028T>C）以及3个先前报道的突变（c.1048 - 1049delGA、c.990delG、整个NHLRC1基因缺失），所有这些突变均位于NHLRC1基因上。两个主要突变（c.1048 - 1049delGA和完整NHLRC1基因缺失）似乎是始祖突变。除了记录LD所观察到的基因异质性外，我们的研究表明，NHLRC1基因突变可能是塞尔维亚/黑山人群中LD的常见病因，主要是由于始祖效应。
