Chromoanasynthesis as a cause of Jacobsen syndrome

Author:

Anzick, Sarah

Thurm, Audrey

Burkett,Sandra

Velez, Daniel

Cho, Elena

Chlebowski, Colby

Virtaneva, Kimmo

Bruno, Daniel

Martin, Clare B

Lang, David M

Brooks, Brian

Martens, Craig

McDermott, David H

Murphy, Philip M [ORCID]
Author Address

Research Technology Branch, National Institute of Allergy and Infectious Diseases, NIH, Bethesda, Maryland, USA., Neurodevelopmental and Behavioral Phenotyping Service, National Institute of Mental Health, NIH, Bethesda, Maryland, USA., Comparative Molecular Cytogenetics Core Facility, Frederick National Laboratory for Cancer Research, National Cancer Institute, NIH, Bethesda, Maryland, USA., Laboratory of Molecular Immunology, National Institute of Allergy and Infectious Diseases, NIH, Bethesda, Maryland, USA., Pediatric Consult Service, Warren Grant Magnuson Clinical Center, NIH, Bethesda, Maryland, USA., Ophthalmic Genetics and Visual Function Branch, National Eye Institute, NIH, Bethesda, Maryland, USA.,

Abstract:

Jacobsen syndrome (MIM #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. © 2020 Wiley Periodicals LLC.

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