Niemann–Pick disease type C (NPC) is a progressive lysosomal storage disorder caused by mutations in the NPC1 (in 95% of cases) or NPC2 (in ~5% of cases) genes, inherited in an autosomal recessive manner. We report the case of a 38-year-old woman with learning disorder from her first year of schooling, and could notice slow progressed cognitive impairment, social withdrawal, apathy, handwriting alterations, deterioration of language skills and dysphagia. Brain magnetic resonance imaging showed severe cerebellar atrophy, hypoplasia of the corpus callosum, asymmetric lateral ventricular enlargement, and severe enlargement of frontal and parietal subarachnoid spaces. Next generation sequencing for NPC genes (NPC1 and NPC2) detected compound heterozygous mutations in NPC1 gene, including c.1553G > A (p.Arg518Gln), paternally inherited, and c.1270C > T (p.Pro424Ser) maternally inherited. The first mutation has been already described in literature and correlated to NPC, while the second mutation is still unknown. Moreover, filipin test and quantification of plasma oxysterols confirmed NPC diagnosis. We can suggest the missense mutation c.1270C > T (p.Pro424Ser) as a new causative mutation of NPC.

中文翻译：

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NPC1基因中新型复合杂合突变导致幼年发病的C型尼曼-皮克病

Niemann-Pick 病 C 型 (NPC) 是一种进行性溶酶体贮积症，由 NPC1（95% 的病例）或 NPC2（约 5% 的病例）基因突变引起，以常染色体隐性方式遗传。我们报告了一名 38 岁女性，从她上学的第一年就患有学习障碍，可能会注意到缓慢进展的认知障碍、社交退缩、冷漠、笔迹改变、语言技能退化和吞咽困难。脑磁共振成像显示严重的小脑萎缩，胼胝体发育不全，不对称的侧脑室扩大，额叶和顶叶蛛网膜下腔严重扩大。NPC 基因（NPC1 和 NPC2）的下一代测序检测到 NPC1 基因中的复合杂合突变，包括 c.1553G > A (p.Arg518Gln)、父系遗传和 c。1270C > T (p.Pro424Ser) 母系遗传。第一个突变已经在文献中描述并与 NPC 相关，而第二个突变仍然未知。此外，菲律宾测试和血浆氧甾醇的定量证实了 NPC 诊断。我们可以建议错义突变 c.1270C > T (p.Pro424Ser) 作为 NPC 的新致病突变。