Singh Shweta, Suzuki Toshimitsu, Uchiyama Akira, Kumada Satoko, Moriyama Nobuko, Hirose Shinichi, Takahashi Yukitoshi, Sugie Hideo, Mizoguchi Koichi, Inoue Yushi, Kimura Kazue, Sawaishi Yukio, Yamakawa Kazuhiro, Ganesh Subramaniam
Department of Biological Sciences and Bioengineering, Indian Institute of Technology, Kanpur, India.
Laboratory for Neurogenetics, RIKEN Brain Science Institute, 2-1, Hirosawa, Wako, Saitama 351-0198, Japan.
J Hum Genet. 2005;50(7):347-352. doi: 10.1007/s10038-005-0263-7. Epub 2005 Jul 15.
Lafora disease (LD) is a rare autosomal recessive genetic disorder characterized by epilepsy, myoclonus, and progressive neurological deterioration. LD is caused by mutations in the EMP2A gene encoding a protein phosphatase. A second gene for LD, termed NHLRC1 and encoding a putative E3 ubiquitin ligase, was recently identified on chromosome 6p22. The LD is relatively common in southern Europe, the Middle East, and Southeast Asia. A few sporadic cases with typical LD phenotype have been reported from Japan; however, our earlier study failed to find EPM2A mutations in four Japanese families with LD. We recruited four new families from Japan and searched for mutations in EPM2A . All eight families were also screened for NHLRC1 mutations. We found five independent families having novel mutations in NHLRC1. Identified mutations include five missense mutations (p.I153M, p.C160R, p.W219R, p.D245N, and p.R253K) and a deletion mutation (c.897insA; p.S299fs13). We also found a family with a ten base pair deletion (c.822-832del10) in the coding region of EPM2A. In two families, no EPM2A or NHLRC1 mutation was found. Our study, in addition to documenting the genetic and molecular heterogeneity observed for LD, suggests that mutations in the NHLRC1 gene may be a common cause of LD in the Japanese population.
拉福拉病（LD）是一种罕见的常染色体隐性遗传疾病，其特征为癫痫、肌阵挛和进行性神经功能衰退。LD由编码一种蛋白磷酸酶的EMP2A基因突变引起。最近在6号染色体p22区域发现了第二个与LD相关的基因，即NHLRC1，它编码一种假定的E3泛素连接酶。LD在南欧、中东和东南亚相对常见。日本曾报道过一些具有典型LD表型的散发病例；然而，我们早期的研究未能在四个患有LD的日本家族中发现EPM2A基因突变。我们从日本招募了四个新家族，并对EPM2A基因进行突变检测。同时对所有八个家族进行NHLRC1基因突变筛查。我们发现五个独立家族在NHLRC1基因中有新的突变。已鉴定的突变包括五个错义突变（p.I153M、p.C160R、p.W219R、p.D245N和p.R253K）和一个缺失突变（c.897insA；p.S299fs13）。我们还发现一个家族在EPM2A基因编码区有一个10个碱基对的缺失（c.822 - 832del10）。在两个家族中，未发现EPM2A或NHLRC1基因突变。我们的研究除了记录了LD所观察到的遗传和分子异质性外，还表明NHLRC1基因突变可能是日本人群中LD的常见病因。
