Department of Dermatologic Surgery, Hospital for Skin Diseases (Institute of Dermatology), Chinese Academy of Medical Sciences and Peking Union Medical College, Nanjing, 210042, Jiangsu, China.
BMC Med Genomics. 2020 Dec 12;13(1):188. doi: 10.1186/s12920-020-00847-1.
Linear nevus sebaceous syndrome (LNSS) is a rare genetic disease characterized by large linear sebaceous nevus typically on the face, scalp, or neck. LNSS could be accompanied by multisystem disorders including the central nervous system. Herein, we report gene mutational profile via whole exome sequencing of both lesional and non-lesional skin samples in a LNSS patient.
A 17-year-old girl presented with multisystem abnormalities, including large skin lesions, ocular disorders, abnormal bone development and neurological symptoms. A diagnosis of LNSS was established based on clinical manifestations, histopathological and imaging findings. The skin lesions were resected and no recurrence was noted at the time of drafting this report. Whole exome sequencing of genomic DNA revealed the following 3 mutations in the lesions of the index patient: KRAS (c.35G > A, p.G12D), PRKRIR (c.A1674T, p.R558S), and RRP7A (c. C670T, p.R224W), but no mutation was found in the healthy skin and peripheral blood sample of the index patient, or in the blood samples of her parents and sibling. PCR-mediated Sanger sequencing of DNA derived from lesional skin sample of the index patient verified KRAS mutation, but not PRKRIR (c.A1674T, p.R558S) and RRP7A (c. C670T, p.R224W). None of the 3 mutations was found in Sanger sequencing in skin lesions of 60 other cases of nevus sebaceous patients.
Our findings show the relevance of KRAS mutation to LNSS, providing new clues in understanding related genetic heterogeneity which could aid genetic counselling for LNSS patients.
线性皮脂腺痣综合征（LNSS）是一种罕见的遗传疾病，其特征为面部、头皮或颈部的大型线性皮脂腺痣。LNSS 可能伴有多种系统疾病，包括中枢神经系统。在此，我们报告了一名 LNSS 患者通过病变和非病变皮肤样本的全外显子组测序发现的基因突变谱。
一名 17 岁女孩表现出多系统异常，包括大面积皮肤病变、眼部疾病、骨骼发育异常和神经症状。根据临床表现、组织病理学和影像学发现，诊断为 LNSS。病变皮肤被切除，在撰写本报告时未发现复发。对该患者病变部位的基因组 DNA 进行全外显子组测序，发现以下 3 个突变：KRAS（c.35G＞A，p.G12D）、PRKRIR（c.A1674T，p.R558S）和 RRP7A（c. C670T，p.R224W），但在患者的健康皮肤和外周血样本以及患者父母和兄弟姐妹的血液样本中均未发现突变。对患者病变皮肤样本的 DNA 进行 PCR 介导的 Sanger 测序验证了 KRAS 突变，但未发现 PRKRIR（c.A1674T，p.R558S）和 RRP7A（c. C670T，p.R224W）突变。在 60 例皮脂腺痣患者的病变皮肤中，Sanger 测序均未发现这 3 个突变。
我们的发现表明 KRAS 突变与 LNSS 相关，为理解相关遗传异质性提供了新的线索，有助于为 LNSS 患者提供遗传咨询。
