Microhomology-Mediated Break-Induced Replication: A Possible Molecular Mechanism of the Formation of a Large CNV in
CNV
FBN1 gene
MMBIR
Marfan syndrome
breakpoint analyses
genomic rearrangement
Journal
Current molecular medicine
ISSN: 1875-5666
Titre abrégé: Curr Mol Med
Pays: Netherlands
ID NLM: 101093076
Informations de publication
Date de publication:
2023
2023
Historique:
received:
14
02
2022
revised:
16
02
2022
accepted:
08
03
2022
medline:
12
4
2023
entrez:
11
4
2023
pubmed:
12
4
2023
Statut:
ppublish
Résumé
Marfan syndrome (MFS) is an autosomal dominant multisystem disorder caused by mutations in the fibrillin-1 gene (FBN1). A small portion of them is copy number variations (CNVs), which can occur through recombination-based, replication-based mechanisms or retrotransposition. Not many have been characterized precisely in MFS. A female patient with suspected Marfan syndrome was referred for genetic testing at our institute. After systematic sequencing of FBN1, TGFBR1, and TGFBR2 genes, multiplex ligation-dependent probe amplification was applied. Long-range PCR, subsequent Sanger sequencing with designed primers, and preliminary in silico analysis were applied for the precise characterization of the breakpoints. Primary analysis displayed a de novo large deletion affecting exons 46 and 47 in the FBN1 gene, which resulted in the loss of the 31st and 32 An increasing number of CNVs are associated with Mendelian diseases and other traits. Approximately 2-7% of the cases in MFS are caused by CNVs. Up to date, hardly any model was proposed to demonstrate the formation of these genomic rearrangements in the FBN1 gene. Hereby, with the help of previous models and breakpoint analysis, we presented a potential mechanism (based on MMBIR) in the formation of this large deletion.
Sections du résumé
BACKGROUND
Marfan syndrome (MFS) is an autosomal dominant multisystem disorder caused by mutations in the fibrillin-1 gene (FBN1). A small portion of them is copy number variations (CNVs), which can occur through recombination-based, replication-based mechanisms or retrotransposition. Not many have been characterized precisely in MFS.
METHODS
A female patient with suspected Marfan syndrome was referred for genetic testing at our institute. After systematic sequencing of FBN1, TGFBR1, and TGFBR2 genes, multiplex ligation-dependent probe amplification was applied. Long-range PCR, subsequent Sanger sequencing with designed primers, and preliminary in silico analysis were applied for the precise characterization of the breakpoints.
RESULTS
Primary analysis displayed a de novo large deletion affecting exons 46 and 47 in the FBN1 gene, which resulted in the loss of the 31st and 32
CONCLUSION
An increasing number of CNVs are associated with Mendelian diseases and other traits. Approximately 2-7% of the cases in MFS are caused by CNVs. Up to date, hardly any model was proposed to demonstrate the formation of these genomic rearrangements in the FBN1 gene. Hereby, with the help of previous models and breakpoint analysis, we presented a potential mechanism (based on MMBIR) in the formation of this large deletion.
Identifiants
pubmed: 37038253
pii: CMM-EPUB-123007
doi: 10.2174/1566524022666220428111943
doi:
Substances chimiques
Fibrillin-1
0
FBN1 protein, human
0
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
433-441Informations de copyright
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