Multigenic truncation of the semaphorin-plexin pathway by a germline chromothriptic rearrangement associated with Moebius syndrome.
Chromosome Breakpoints
Chromothripsis
Fatal Outcome
Gene Rearrangement
Germ-Line Mutation
High-Throughput Nucleotide Sequencing
Humans
Intracellular Signaling Peptides and Proteins
/ genetics
Male
Membrane Glycoproteins
/ genetics
Middle Aged
Mobius Syndrome
/ genetics
Semaphorin-3A
/ genetics
Semaphorins
/ genetics
Moebius syndrome
PIK3CG
SEMA3A
SEMA3D
chromothripsis
Journal
Human mutation
ISSN: 1098-1004
Titre abrégé: Hum Mutat
Pays: United States
ID NLM: 9215429
Informations de publication
Date de publication:
08 2019
08 2019
Historique:
received:
23
10
2018
revised:
17
04
2019
accepted:
24
04
2019
pubmed:
30
4
2019
medline:
31
3
2020
entrez:
30
4
2019
Statut:
ppublish
Résumé
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.
Identifiants
pubmed: 31033088
doi: 10.1002/humu.23775
pmc: PMC6688968
mid: NIHMS1026324
doi:
Substances chimiques
Intracellular Signaling Peptides and Proteins
0
Membrane Glycoproteins
0
PLXND1 protein, human
0
SEMA3A protein, human
0
Semaphorin-3A
0
Semaphorins
0
Types de publication
Case Reports
Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
1057-1062Subventions
Organisme : University of Copenhagen Excellence Programme for Interdisciplinary Research (Global Genes, Local Concerns)
Pays : International
Organisme : Cancer Prevention Research Institute of Texas (CPRIT) Recruitment Award
Pays : International
Organisme : NIH K99/R00 Pathway to Independence Award (NIGMS)
Pays : International
Organisme : Lundbeckfonden
ID : 2013-14290
Pays : International
Organisme : NIGMS NIH HHS
ID : R00 GM119126
Pays : United States
Organisme : Danish Council for Independent Research
Pays : International
Organisme : Det Frie Forskningsråd
ID : 4183-00482B
Pays : International
Informations de copyright
© 2019 Wiley Periodicals, Inc.
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