AUTHOR=Marsan Marina , Brutti Mattia , Meloni F. , Marica M. , Soddu C. , Lai F. , Martorana D. , Savasta S. 

TITLE=A novel missense variant of FBN1 gene in a Sardinian family with Marfan syndrome: a case report

JOURNAL=Frontiers in Pediatrics

VOLUME=Volume 13 - 2025

YEAR=2025

URL=https://www.frontiersin.org/journals/pediatrics/articles/10.3389/fped.2025.1549504

DOI=10.3389/fped.2025.1549504

ISSN=2296-2360

ABSTRACT=BackgroundMarfan Syndrome (MS) is a connective tissue disorder, an autosomal dominant condition mostly caused by variants in the FBN1 gene, which encodes for fibrillin-1 protein. Anomalies in the gene lead to a wide variety of clinical manifestations, including disorders of the cardiac, ocular and musculoskeletal system. We present a case of a child belonging to a Sardinian family of four generations, with a novel variant found in the FBN1 gene.ObjectiveTo include this novel missense FBN1 variant into genetic counselling for Marfan Syndrome and to discuss its genotypic-phenotypic correlation.MethodsFirstly, the proband was diagnosed with Marfan Syndrome using 2020 Revised Ghent Criteria, and she then underwent genetic testing using Next Generation sequencing.ResultsThe NGS revealed a novel heterozygous missense variant (c.2348A>G) in the FBN1 gene, in exon 20. This genetic variant caused a missense substitution of a serine residue with an arginine residue in the position 783 of Fibrillin-1 protein. The variant was then evaluated in the other family members, and was eventually only found in symptomatic individuals, regardless of the severity of their phenotype, demonstrating the segregation with MS; furthermore, it showed complete penetrance with the disease.ConclusionsOur results suggest that this variant is responsible for MS and it therefore should be included in genetic diagnoses and counselling discussion.