论文部分内容阅读
目的报告在2例婴儿型神经元蜡样质脂褐素沉积病中发现棕榈酰蛋白硫酯酶1 (PPT1)基因2个新的突变。方法先证者1和2均在1岁以内出现进行性智能和运动发育倒退。病理检查诊断为婴儿型神经元蜡样质脂褐素沉积病。对先证者1和2以及前者的父母的PPT1基因编码区9个外显子及两旁的内含子序列设计引物进行PCR扩增,扩增产物测序检查。结果先证者1存在复合杂合突变,分别为第6外显子的c550G→A即E184K点突变和第1内含子的IVS1+1G→A剪接突变。其父亲在第1内含子也存在IVS1+1G→A杂合性剪接突变,其母存在E184K杂合性突变。先证者2存在纯合突变,在第3外显子出现c272A→C即Q91P突变。对50例正常人DNA进行突变筛查均未发现相同突变。结论PPT1基因在第1内含子的IVS1+1G→A剪接突变以及第3外显子的Q91P突变为2个以前没有报道的新突变,导致婴儿型神经元蜡样质脂褐素沉积病的发生。因此中国人的婴儿型神经元蜡样质脂褐素沉积病在PPT1基因的突变类型方面和其他地区的病例可能不完全相同。
PURPOSE: Two novel mutations in the palmitoyl-S-acetylthiolase 1 (PPT1) gene have been reported in two infantile neuronal wax-like lipofuscinosis deposits. Method Proofs 1 and 2 were within 1 year of progressive intellectual and motor development retrograde. Pathological examination was diagnosed as infantile neuronal wax-like lipofuscin deposition disease. Primers 1 and 2 and parents of the former PPT1 gene coding region 9 exons and introns on both sides of the primers designed primers for PCR amplification, amplification products sequencing. Results There was a composite heterozygous mutation in proband 1, which was c550G → A of exon 6, E184K point mutation and IVS1 + 1G → A splicing mutation of intron 1 respectively. His father in the first intron also exists IVS1 + 1G → A heterozygous splicing mutations, the mother there E184K heterozygous mutation. There is a homozygous mutation in proband 2, and a c272A → C Q91P mutation in exon 3. Mutation screening of 50 normal human DNA did not find the same mutation. Conclusion The IVT1 + 1G → A splice mutation of PPT1 gene in exon 1 and the Q91P mutation in exon 3 of the PPT1 gene are two new mutations that have not been reported before, leading to the neuronal wax-like lipofuscin deposition disease occur. Therefore, the Chinese infant neuron wax-like lipofuscin deposition disease in the type of mutations in the PPT1 gene and other cases may not be the same.