Marfan syndrome (MFS) is a life-threatening autosomal dominant genetic disorder of connective tissue caused by the pathogenic mutation of FBN1. Whole exome sequencing and Sanger sequencing were performed to identify the pathogenic mutation. The transcriptional consequence of the splice-altering mutation was analyzed via minigene assays and reverse-transcription PCR. We identified a novel pathogenic mutation (c.8051+1G>C) in the splice site of exon 64 of the FBN1 gene in an MFS-pedigree. This mutation was confirmed to cause two different truncated transcripts (entire exon 64 skipping; partial exon 64 exclusion). We also systematically summarized previously reported transcriptional studies of pathogenic splice-altering mutations in the FBN1 gene to investigate the clinical and transcriptional consequences. In conclusion, we reported for the first time that a splice-altering mutation in the FBN1 gene leads to two abnormal transcripts simultaneously.
Keywords: FBN1; Marfan syndrome; genetic diagnosis; splicing mutation; whole-exome sequencing.