%0 Case Reports
%T Multigenic truncation of the semaphorin-plexin pathway by a germline chromothriptic rearrangement associated with Moebius syndrome.
%A Nazaryan-Petersen L
%A Oliveira IR
%A Mehrjouy MM
%A Mendez JMM
%A Bak M
%A Bugge M
%A Kalscheuer VM
%A Bache I
%A Hancks DC
%A Tommerup N
%J Hum Mutat
%V 40
%N 8
%D 08 2019
%M 31033088
%F 4.7
%R 10.1002/humu.23775
%X 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.