Chromoanasynthesis as a cause of Jacobsen Syndrome

Jacobsen syndrome (OMIM #147791) is a rare multisystem genomic disorder involving craniofacial abnormalities, intellectual disability, other neurodevelopmental defects and terminal truncation of chromosome 11q, typically deleting ~170 to >340 genes. We describe the first case of Jacobsen syndrome caused by congenital chromoanasynthesis, an extreme form of complex chromosomal rearrangement. Six duplications and five deletions occurred on one copy of chromosome 11q with microhomology signatures in the breakpoint junctions, indicating an all-at-once replication-based rearrangement mechanism in a gametocyte or early post-zygotic cell. Eighteen genes were deleted from the Jacobsen region, including KIRREL3, which is associated with intellectual disability. Patients of any age with abnormal immune function who have recurrent or unusual infections, whose blood tests show evidence of immune dysfunction, or who have GVHD, XSCID, CGD or LAD may be eligible... (for more see dbGaP study page.)

雅各布森综合征（OMIM #147791）是一种罕见的多系统基因组紊乱疾病，可引发颅面畸形、智力障碍及其他神经发育缺陷，伴随11号染色体长臂末端截短，通常会删除约170至340余个基因。本研究报道了首例由先天性染色体合成异常（chromoanasynthesis）——一种极端复杂的染色体重排类型——引发的雅各布森综合征病例。该病例中，11号染色体长臂的其中一条拷贝发生了6次重复与5次缺失，断点连接处存在微同源特征，提示该重排是在配子细胞或合子后早期细胞中通过一次性复制依赖机制完成的。雅各布森综合征相关区域共缺失18个基因，其中包括与智力障碍相关的KIRREL3基因。任何年龄段的免疫功能异常患者，若存在复发性或不典型感染、血液检测提示免疫功能紊乱，或患有移植物抗宿主病（GVHD）、X连锁重症联合免疫缺陷（XSCID）、慢性肉芽肿病（CGD）、白细胞粘附缺陷症（LAD），均可能符合入组条件……（更多详情请参见基因型与表型数据库（dbGaP）研究页面）