Compound heterozygous mutations in FBN1 in a large family with Marfan syndrome.

ABSTRACT:

Background

Marfan syndrome (MFS) is a dominant monogenic disorder caused by mutations in fibrillin 1 (FBN1). Rarely, compound heterozygosity for FBN1 mutations has been described.

Methods

A large kindred with MFS was assessed clinically over decades, and genetically using exome and/or Sanger sequencing.

Results

A previously identified FBN1 missense variant (p.Tyr754Cys) was confirmed in all subjects with MFS. An additional variant (p.Met2273Thr), previously associated with incomplete MFS, was identified in three siblings. These three compound heterozygous individuals had aortic dilatation at early age (all <30 years): one also had cerebral and ocular aneurysms; and one, who had undergone surgical repair aged 18 years, died from aortic dissection at 31 years. In contra

SUBMITTER: McInerney-Leo AM 

PROVIDER: S-EPMC7057098 | biostudies-literature | 2020 Mar

REPOSITORIES: biostudies-literature