Novel mutation in the NHLRC1 gene in a Malian family with a severe phenotype of Lafora disease
Novel mutation in the NHLRC1 gene in a Malian family with a severe phenotype of Lafora disease
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DOI：
10.1007/s10048-009-0190-4
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发表时间：
2009-10-01
期刊：
影响因子：
2.2
通讯作者：
Fischbeck, K. H.
中科院分区：
文献类型：
--
作者：
Traore, M.;Landoure, G.;Fischbeck, K. H.
我们研究了一个有父母血缘关系的马里家庭和八个兄弟姐妹中的两个，他们患有儿童晚期起病的进行性肌阵挛癫痫和认知能力下降，这与拉福拉病的诊断一致。遗传分析显示，在NHLRC1基因中发现了一个新的纯合单核苷酸变异，C.560A和GT；C，产生错义改变H187P。改变的氨基酸是高度保守的，突变会削弱Malin在体外降解拉福林的能力。病理检查显示拉福拉病可累及全脑，尤其累及苍白球、丘脑和小脑。我们的发现证明，拉福拉病在西非人口中具有严重的表现。
We studied a Malian family with parental consanguinity and two of eight siblings affected with late-childhood-onset progressive myoclonus epilepsy and cognitive decline, consistent with the diagnosis of Lafora disease. Genetic analysis showed a novel homozygous single-nucleotide variant in the NHLRC1 gene, c.560A > C, producing the missense change H187P. The changed amino acid is highly conserved, and the mutation impairs malin's ability to degrade laforin in vitro. Pathological evaluation showed manifestations of Lafora disease in the entire brain, with particularly severe involvement of the pallidum, thalamus, and cerebellum. Our findings document Lafora disease with severe manifestations in the West African population.