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

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

Research output: Contribution to journalArticle

1 Citation (Scopus)

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.

Original languageEnglish (US)
Pages (from-to)1057-1062
Number of pages6
JournalHuman Mutation
Volume40
Issue number8
DOIs
StatePublished - Jan 1 2019

Fingerprint

Mobius Syndrome
Abducens Nerve
Congenital, Hereditary, and Neonatal Diseases and Abnormalities
Facial Nerve
Paralysis
Computer Simulation
Genes
Mutation
Proteins

Keywords

  • chromothripsis
  • Moebius syndrome
  • PIK3CG
  • SEMA3A
  • SEMA3D

ASJC Scopus subject areas

  • Genetics
  • Genetics(clinical)

Cite this

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

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; Tommerup, Niels.

In: Human Mutation, Vol. 40, No. 8, 01.01.2019, p. 1057-1062.

Research output: Contribution to journalArticle

Nazaryan-Petersen, L, Oliveira, IR, Mehrjouy, MM, Mendez, JMM, Bak, M, Bugge, M, Kalscheuer, VM, Bache, I, Hancks, D & Tommerup, N 2019, 'Multigenic truncation of the semaphorin–plexin pathway by a germline chromothriptic rearrangement associated with Moebius syndrome', Human Mutation, vol. 40, no. 8, pp. 1057-1062. https://doi.org/10.1002/humu.23775
Nazaryan-Petersen, Lusine ; Oliveira, Inês R. ; Mehrjouy, Mana M. ; Mendez, Juan M.M. ; Bak, Mads ; Bugge, Merete ; Kalscheuer, Vera M. ; Bache, Iben ; Hancks, Dustin ; Tommerup, Niels. / Multigenic truncation of the semaphorin–plexin pathway by a germline chromothriptic rearrangement associated with Moebius syndrome. In: Human Mutation. 2019 ; Vol. 40, No. 8. pp. 1057-1062.
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