METHODS: Here, we report two patients (father and daughter) in a Chinese family (for the first time) with germline KIT mutation, and described their pathology, genetics and clinical manifestations. A 25-year-old Chinese woman went to hospital because of abdominal pain, and computed tomography showed multiple tumors in the small intestine. Small pigmented spots appeared on the skin within a few months after birth. Her father also had multiple pigmented spots and a history of multifocal GISTs. Multiple GISTs associated with diffuse interstitial Cajal cells (ICCs) hyperplasia were positive for CD117 and DOG-1. Gene sequencing revealed a germline mutation at codon 560 of exon 11 (p.V560G) of KIT gene in these two patients. Imatinib therapy showed the long-lasting disease stability after resection. Remarkably, the hypopigmentation of the skin could also be observed. Luckily germline KIT mutation has not been identified yet in the 3-year-old daughter of the female patient.
CONCLUSIONS: Diagnosis of familial GISTs depends on combination of diffuse ICCs hyperplasia, germline KIT/PDGFRA mutation, hyperpigmentation and family history.
方法:这里,我们报告了中国家庭中的两名患者(父亲和女儿)(首次)具有种系KIT突变,并描述了他们的病理,遗传学和临床表现。一名25岁的中国妇女因腹痛而去医院,计算机断层扫描显示小肠有多个肿瘤。出生后几个月内皮肤上出现小色斑。她的父亲也有多个色斑和多灶性GIST的历史。与弥漫性间质Cajal细胞(ICC)增生相关的多个GIST对CD117和DOG-1呈阳性。基因测序显示外显子11的密码子560处存在种系突变(第这两种患者的KIT基因V560G)。伊马替尼治疗显示切除后疾病的长期稳定性。值得注意的是,还可以观察到皮肤的色素沉着不足。幸运的是,女性患者3岁的女儿尚未发现种系KIT突变。
结论:家族性GIST的诊断取决于弥漫性ICC增生的组合,种系试剂盒/PDGFRA突变,色素沉着和家族史。