PDF(Pubmed)
Abstract：
Noonan syndrome is an autosomal dominant disease characterized by multi-organ disorders caused by variants of genes involved in the RAS/MAPK signaling pathway. The nine causative genes including PTPN11 and CBL have been identified. Mastocytosis is a disease characterized by mast cell proliferation in skin, bone marrow, and other organs. To date, no previous cases of Noonan syndrome with mastocytosis caused by a pathogenic CBL variant have been reported. A boy was diagnosed with Noonan syndrome at 8 months of age with facial features and minor anomaly of his body. He presented with brown nodules of 5-10 mm on his body since the age of 2 months. The patient was diagnosed with mastocytosis by a biopsy specimen from brown nodules, which showed infiltration of mast cells. Whole-exome sequencing of the parent-patient trio revealed a de novo pathogenic CBL variant. The occurrence of mastocytosis may be a cue for the analysis of the CBL gene in Noonan syndrome. The CBL gene is involved in mastocytosis and various cancers. In the case of the pathogenic variant, long-term follow-up for the risk of cancers related to the CBL variant is necessary.
摘要：
Noonan综合征是一种常染色体显性疾病，其特征是由RAS/MAPK信号通路中涉及的基因变异引起的多器官疾病。已经鉴定了包括PTPN11和CBL在内的9个致病基因。肥大细胞增多症是一种以肥大细胞增生为特征的皮肤疾病,骨髓,和其他器官。迄今为止,以前没有报道过由致病性CBL变异体引起的Noonan综合征伴肥大细胞增多症的病例.一名男孩在8个月大时被诊断出患有Noonan综合征，面部特征和身体轻微异常。自2个月大以来，他的身体上出现了5-10毫米的棕色结节。该患者通过棕色结节的活检标本被诊断为肥大细胞增多症，显示肥大细胞浸润。父母三人组的全外显子组测序显示了从头致病性CBL变体。肥大细胞增多症的发生可能是Noonan综合征CBL基因分析的线索。CBL基因与肥大细胞增多症和各种癌症有关。在致病变异的情况下，有必要对与CBL变异相关的癌症风险进行长期随访.
