Chromoanasynthesis as a cause of Jacobsen Syndrome. 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（Jacobsen syndrome，OMIM #147791）是一种罕见的多系统基因组疾病，以颅面部畸形、智力障碍、其他神经发育缺陷及11号染色体长臂末端截短为核心特征，通常会缺失约170至340余个基因。本研究报道了首例由先天性染色体复制重排（chromoanasynthesis）引发的雅各布森综合征病例，该病变属于复杂染色体重排的极端类型。研究发现，11号染色体长臂的一条同源拷贝上发生了6次染色体片段重复与5次片段缺失，断点连接处存在微同源序列特征，提示该重排事件是在配子细胞或合子早期通过一次性完成的复制依赖型重排机制形成的。雅各布森综合征关键区域共有18个基因被删除，其中包括与智力障碍相关的KIRREL3基因。任何年龄阶段、存在免疫功能异常且伴反复或罕见感染、血液检测提示免疫功能紊乱，或罹患移植物抗宿主病（GVHD，Graft-versus-host disease）、X连锁重症联合免疫缺陷（XSCID，X-linked severe combined immunodeficiency）、慢性肉芽肿病（CGD，chronic granulomatous disease）或白细胞粘附缺陷症（LAD，leukocyte adhesion deficiency）的患者，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，Database of Genotypes and Phenotypes）研究页面）