FBN1 Splice-Altering Mutations in Marfan Syndrome: A Case Report and Literature Review

Area of Science:

• Genetics
• Molecular Biology
• Medical Science

Background:

• Marfan syndrome (MFS) is a severe genetic connective tissue disorder.
• It is caused by mutations in the FBN1 gene, affecting fibrillin-1 production.
• Understanding mutation consequences is crucial for MFS diagnosis and treatment.

Approach:

• Whole exome and Sanger sequencing identified a novel FBN1 splice-site mutation (c.8051+1G>C).
• Minigene assays and RT-PCR analyzed the transcriptional impact of the mutation.
• Previous FBN1 transcriptional studies were systematically reviewed.

Key Points:

• A novel pathogenic splice-altering mutation in FBN1 (c.8051+1G>C) was identified in an MFS family.
• This mutation leads to two distinct aberrant transcripts: complete exon 64 skipping and partial exon 64 exclusion.
• This is the first report of a single FBN1 splice-altering mutation causing two abnormal transcripts concurrently.

Conclusions:

• The identified FBN1 mutation is pathogenic and causes Marfan syndrome.
• The mutation results in complex alternative splicing, producing truncated fibrillin-1.
• This finding deepens the understanding of genotype-phenotype correlations in Marfan syndrome.