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Chromoanasynthesis as a cause of Jacobsen syndrome
Author(s) -
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.
Publication year - 2020
Publication title -
american journal of medical genetics part a
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.064
H-Index - 112
eISSN - 1552-4833
pISSN - 1552-4825
DOI - 10.1002/ajmg.a.61824
Subject(s) - breakpoint , chromothripsis , genetics , intellectual disability , biology , craniofacial , chromosome , craniofacial abnormality , chromosomal rearrangement , gene , karyotype , genome instability , dna , dna damage
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.