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

Abstract

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.

Reassessment of genes associated with dilated and hypertrophic cardiomyopathy in a Chinese Han population

“…Serum carbohydrate antigen 125 level is reportedly correlated with DCM prognosis and clinical severity [17,18] . FBN1 was mostly reported as a causal gene of Marfan syndrome [19,20] while in this study, we found the association of FBN1 and DCM, which will be reported in another work of our team. RYR2 was mostly known as a well-established causal gene of catecholaminergic polymorphic ventricular tachycardia [21] .…”

Establishment and analysis of artificial neural network diagnosis model for coagulation-related molecular subgroups in coronary artery disease

“…In addition, CYP2B6 is the only gene encoding a functional enzyme in the human CYP2B subfamily (Desta et al, 2021), genetic variation in this gene locus affects the metabolism or bioactivation of clinically important drugs bupropion (Kirchheiner et al, 2003) and efavirenz (Haas et al, 2004;Desta et al, 2007). Pathogenic mutations in FBN1 are the cause of Marfan syndrome, a lifethreatening autosomal dominant disorder of connective tissue (Wang et al, 2022). Lipoma HMGIC fusion partner-like 5 (LHFPL5) is an important molecule in the normal auditory system involved in mechanotransduction pathways in sensory hair cells of the ear (Yu et al, 2020).…”

Editorial for the Molecular Genetics and Genomics of Metabolic Disorders in Cardiovascular and Cerebrovascular Diseases Special Issue: June 2023

“…Previous molecular genetic studies have demonstrated that MED12 gene mutations can lead to inherited diseases, and this study presents the MED12 gene as a potential target for the prevention and treatment of AD. In another study in this Special Issue, Wang et al [ 3 ] pay attention to the pathogenic gene FBN1 in Marfan syndrome (MFS), which is a highly penetrant and lethal autosomal dominant genetic disorder. Gene FBN1 , which encodes the extracellular matrix glycoprotein fibrillin-1, is the main pathogenic gene of MFS.…”