癌症驱动基因的体细胞突变被发现与血管畸形有关，其临床表现范围从皮肤胎记到威胁生命的全身异常。迄今为止，在中国人群中仅报道了有限数量的病例和突变。本研究旨在描述一组中国儿科血管畸形患者的体细胞突变谱。收集了2019年5月至2020年10月期间在北京儿童医院诊断为各种血管畸形的儿科患者。提取每位患者皮肤病变的基因组DNA，并通过全外显子测序鉴定致病体细胞突变。变异等位基因频率低于5%的突变经过超深度测序验证。共分析了67名儿科患者（男性33名，女性34名，年龄范围：0.1-14.8岁）。外显子组测序鉴定出53名患者对应基因的体细胞突变，分子诊断率为79.1%。PIK3CA突变中，有29个是热点突变 p.E542K、p.E545K 和 p.H1047R/L，非热点突变在与PIK3CA相关的过度生长谱患者中很常见，占检测到的突变的50.0%（11/22）。热点突变 GNAQ p.R183Q 和 TEK p.L914F 分别与大部分葡萄酒斑/斯图尔格-韦伯综合征和静脉畸形有关。此外，我们在Proteus综合症中鉴定出一种新的 AKT1 p.Q79K 突变，以及在疣状静脉畸形中鉴定出 MAP3K3 p.E387D 突变。中国人群的血管畸形体细胞突变谱与其他人群报道的相似，但非热点 PIK3CA 突变也可能很常见。分子诊断可能有助于儿科血管畸形患者的临床诊断、治疗和管理。 © 2023. Institut National de la Santé et de la Recherche Médicale (INSERM).

Somatic mutations of cancer driver genes are found to be responsible for vascular malformations with clinical manifestations ranging from cutaneous birthmarks to life-threatening systemic anomalies. Till now, only a limited number of cases and mutations were reported in Chinese population. The purpose of this study was to describe the somatic mutation spectrum of a cohort of Chinese pediatrics with vascular malformations.Pediatrics diagnosed with various vascular malformations were collected between May 2019 and October 2020 from Beijing Children's Hospital. Genomic DNA of skin lesion of each patient was extracted and sequenced by whole-exome sequencing to identify pathogenic somatic mutations. Mutations with variant allele frequency less than 5% were validated by ultra-deep sequencing.A total of 67 pediatrics (33 males, 34 females, age range: 0.1-14.8 years) were analyzed. Exome sequencing identified somatic mutations of corresponding genes in 53 patients, yielding a molecular diagnosis rate of 79.1%. Among 29 PIK3CA mutations, 17 were well-known hotspot p.E542K, p.E545K and p.H1047R/L. Non-hotspot mutations were prevalent in patients with PIK3CA-related overgrowth spectrum, accounting for 50.0% (11/22) of detected mutations. The hotspot GNAQ p.R183Q and TEK p.L914F mutations were responsible for the majority of port-wine stain/Sturge-Weber syndrome and venous malformation, respectively. In addition, we identified a novel AKT1 p.Q79K mutation in Proteus syndrome and MAP3K3 p.E387D mutation in verrucous venous malformation.The somatic mutation spectrum of vascular malformations in Chinese population is similar to that reported in other populations, but non-hotspot PIK3CA mutations may also be prevalent. Molecular diagnosis may help the clinical diagnosis, treatment and management of these pediatric patients with vascular malformations.© 2023. Institut National de la Santé et de la Recherche Médicale (INSERM).