Phenotype Presentation for a Novel Mutation Affecting a Conserved Cysteine Residue in Exon 63 of Fibrillin-1 (Cys2633Arg)

Marfan syndrome is an autosomal dominant disease caused by mutations in the gene encoding for fibrillin-1 ( FBN1 ). More than 1,000 FBN1 mutations have been identified, which may lead to multiple organ involvement, particularly of the ocular, skeletal, and cardiovascular systems. Mutations in exons...

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Bibliographic Details
Published in:Biochemical genetics 2014-06, Vol.52 (5-6), p.225-232
Main Authors: Stevic, Ivan, Kozenko, Mariya, LoStracco, Robert, Chan, Anthony K. C., Chan, Howard H. W.
Format: Article
Language:English
Subjects:
Adult
Amino Acid Sequence
Biochemistry
Biomedical and Life Sciences
Biomedicine
Cardiovascular system
Conserved Sequence
Cysteine - genetics
Exons
Female
Fibrillin-1
Fibrillins
Genetic Association Studies
Human Genetics
Humans
Male
Marfan Syndrome - genetics
Medical Microbiology
Microfilament Proteins - genetics
Middle Aged
Mutation
Pedigree
Phenotype
Zoology
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Summary:Marfan syndrome is an autosomal dominant disease caused by mutations in the gene encoding for fibrillin-1 ( FBN1 ). More than 1,000 FBN1 mutations have been identified, which may lead to multiple organ involvement, particularly of the ocular, skeletal, and cardiovascular systems. Mutations in exons 59–65 have been reported in the past to cause mild Marfan-like fibrillinopathies. We report a family with a mutation in exon 63 that manifests with significant cardiovascular system involvement such as aortic root dilatations, dissection of the aorta, and sudden death at a young age. Genetic analysis revealed that four related individuals are positive for a novel heterozygous Cys2633Arg mutation in exon 63. Their genotype–phenotype profile (based on the revised Ghent nosology) is described. We postulate that the Cys2633Arg mutation may manifest with significant and progressive enlargement of the aortic root, risk of aortic dissections, and minor skeletal abnormalities, without involving the ocular system (i.e., ectopia lentis).
ISSN:0006-2928
1573-4927
DOI:10.1007/s10528-014-9642-0