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Abstract：
As one of the epidermal nevus syndromes, Schimmelpenning-Feuerstein-Mims (SFM) is characterized by craniofacial nevus sebaceous (NS) and extracutaneous abnormalities (e.g., brain, eyes, and bone). Here, we report a case of a 4-year-old boy who presented with significant skin abnormalities (NS in the scalp, extensive epidermal nevus along Blaschko\'s lines), ocular abnormalities (strabismus), central nervous system abnormalities (seizure and mental retardation), lymphatic dysplasia (chylous pleural and pericardial effusion), cardiac abnormalities (patent foramen ovale), urogenital system abnormalities (cryptorchidism, hypospadias), and a tumor predisposition (embryonal rhabdomyosarcoma). DNA samples from NS, rhabdomyosarcoma, and peripheral blood leukocytes were analyzed by next-generation sequencing. A novel mutation in the HRAS gene (c.38G>T; p.Gly13Val) was detected in a mosaic state in NS, rhabdomyosarcoma, and peripheral blood leukocytes, with different ratio of heterozygous mutation (HRAS c.38G>T) of 39.90% (9412/23 588 reads), 73.03% (205 562/281 468 reads), and 14.16% (15 837/111 842 reads), respectively. By predicting the impact of the mutation on the biological function of protein, we found that the novel HRAS mutation (c.38G>T; p.Gly13Val) had the highest damaging scores among other HRAS mutations reported so far. This is the first reported SFM syndrome patient with novel mosaic HRAS mutation, which may help to expand the mutational spectrum of HRAS and better understand the role of HRAS in the disease.
摘要：
作为表皮痣综合征之一，Schimmelpenning-Feuerstein-Mims（SFM）的特征是颅面痣皮脂腺（NS）和皮肤外异常（例如，大脑,眼睛,和骨头）。这里,我们报告了一个4岁男孩的病例，该男孩表现出明显的皮肤异常（头皮中的NS，沿着Blaschko线广泛的表皮痣)，眼部异常（斜视），中枢神经系统异常（癫痫发作和智力低下），淋巴发育不良（乳糜胸膜和心包积液），心脏异常（卵圆孔未闭），泌尿生殖系统异常（隐睾，尿道下裂)，和肿瘤易感性（胚胎性横纹肌肉瘤）。来自NS的DNA样本，横纹肌肉瘤,和外周血白细胞通过下一代测序进行分析。在NS的镶嵌状态下检测到HRAS基因的新突变（c.38G>T;p.Gly13Val），横纹肌肉瘤,和外周血白细胞，具有不同比例的39.90%(9412/23.588读段)的杂合突变(HRASc.38G>T)，73.03%（205.562/281.468读数），和14.16%（15.837/111.842读数），分别。通过预测突变对蛋白质生物学功能的影响,我们发现新的HRAS突变(c.38G>T;p.Gly13Val)在迄今报道的其他HRAS突变中具有最高的损伤评分.这是首例报道的具有新型马赛克HRAS突变的SFM综合征患者，这可能有助于扩大HRAS的突变谱，更好地了解HRAS在疾病中的作用。
