Multigenic truncation of the semaphorin-plexin pathway by a germline 
chromothriptic rearrangement associated with Moebius syndrome

Nazaryan-Petersen, Lusine; Oliveira, Inês R.; Mehrjouy, Mana M.; Mendez, Juan M. M.; Bak, Mads; Bugge, Merete; Kalscheuer, Vera M.; Bache, Iben; Hancks, Dustin C.; Tommerup, Niels

doi:10.1002/humu.23775

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Multigenic truncation of the semaphorin-plexin pathway by a germline chromothriptic rearrangement associated with Moebius syndrome

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Kalscheuer, Vera M.
Chromosome Rearrangements and Disease (Vera Kalscheuer), Research Group Development & Disease (Head: Stefan Mundlos), Max Planck Institute for Molecular Genetics, Max Planck Society;

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Citation

Nazaryan-Petersen, L., Oliveira, I. R., Mehrjouy, M. M., Mendez, J. M. M., Bak, M., Bugge, M., et al. (2019). Multigenic truncation of the semaphorin-plexin pathway by a germline chromothriptic rearrangement associated with Moebius syndrome. Human Mutation, 40(8), 1057-1062. doi:10.1002/humu.23775.

Cite as: https://hdl.handle.net/21.11116/0000-0009-2A6E-E

Abstract

Moebius syndrome (MBS) is a congenital disorder caused by paralysis of the facial and abducens nerves. Although a number of candidate genes have been suspected, so far only mutations in PLXND1 and REV3L are confirmed to cause MBS. Here, we fine mapped the breakpoints of a complex chromosomal rearrangement (CCR) 46,XY,t(7;8;11;13) in a patient with MBS, which revealed 41 clustered breakpoints with typical hallmarks of chromothripsis. Among 12 truncated protein-coding genes, SEMA3A is known to bind to the MBS-associated PLXND1. Intriguingly, the CCR also truncated PIK3CG, which in silico interacts with REVL3 encoded by the other known MBS-gene REV3L, and with the SEMA3A/PLXND1 complex via FLT1. Additional studies of other complex rearrangements may reveal whether the multiple breakpoints in germline chromothripsis may predispose to complex multigenic disorders.