A Novel Heterozygous Intronic FBN1 Variant Contributes to Aberrant RNA Splicing in Marfan Syndrome.
Mol Genet Genomic Med
; 12(9): e70004, 2024 Sep.
Article
em En
| MEDLINE
| ID: mdl-39219382
ABSTRACT
BACKGROUND:
Marfan syndrome (MFS) is a complex genetic systemic connective tissue disorder. It is well known that genetic factors play a critical role in the progression of MFS, with nearly all cases attributed to variants in the FBN1 gene.METHODS:
We investigated a Chinese family with MFS spanning two generations. Whole exome sequencing, in silico analysis, minigene constructs, transfection, RT-PCR, and protein secondary structure analysis were used to analyze the genotype of the proband and his father.RESULTS:
The main clinical manifestations of the proband and his father were subluxation of the left lens and high myopia with pectus deformity. Whole exome sequencing identified a novel single nucleotide variant (SNV) in the FBN1 gene at a non-canonical splice site, c.443-3C>G. This variant resulted in two abnormal mRNA transcripts, leading to a frameshift and an in-frame insertion. Further in vitro experiments indicated that the c.443-3C>G variant in FBN1 was pathogenic and functionally harmful.CONCLUSION:
This research identified a novel intronic pathogenic FBN1 c.443-3C>G gene variant, which led to two different aberrant splicing effects. Further functional analysis expands the variant spectrum and provides a strong indication and sufficient basis for preimplantation genetic testing for monogenic disease (PGT-M).Palavras-chave
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Base de dados:
MEDLINE
Assunto principal:
Linhagem
/
Íntrons
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Splicing de RNA
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Fibrilina-1
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Heterozigoto
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Síndrome de Marfan
Idioma:
En
Ano de publicação:
2024
Tipo de documento:
Article