Homozygosity for a missense mutation in fibulin-5 (FBLN5) results in a severe form of cutis laxa.

Abstract

Hereditary cutis laxa comprises a heterogeneous group of connective tissue disorders characterized by loose skin and variable systemic involvement. Autosomal dominant and recessive as well as X-linked forms have been described. Some dominant forms are caused by mutations in the elastine gene (ELN). The X-linked form is now classified in the group of copper transport diseases. The genetic defect underlying the autosomal recessive (AR) forms of cutis laxa is not known. The phenotypic abnormalities recently observed in a fibulin-5 knockout mouse model are reminiscent of human AR cutis laxa type I. Both share cutis laxa, lung emphysema and arterial involvement. Molecular study of the fibulin-5 (FBLN5) gene in a large consanguineous Turkish family with four patients affected by AR cutis laxa type I demonstrated the presence of a homozygous missense mutation (T998C) in the FBLN5 gene resulting in a serine-to-proline (S227P) substitution in the fourth calcium-binding epidermal growth factor-like domain of fibulin-5 protein. This amino acid substitution is predicted to have important structural and functional consequences for normal elastogenesis. As such, we provide evidence that a genetic defect in fibulin-5 (FBLN5, also known as EVEC or DANCE) is responsible for a recessive form of cutis laxa in humans.

• Authors: Bart Loeys, Lionel Van Maldergem, Geert Mortier, Paul Coucke, Sabine Gerniers, Jean-Marie Naeyaert, Anne De Paepe
• Journal: Human molecular genetics (Hum Mol Genet) Vol. 11 Issue 18 Pg. 2113-8 (Sep 01 2002) ISSN: 0964-6906 [Print] England
• PMID: 12189163 (Publication Type: Case Reports, Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Extracellular Matrix Proteins
• FBLN5 protein, human
• Recombinant Proteins

Topics

• Cutis Laxa (genetics)
• Disease Progression
• Extracellular Matrix Proteins (genetics)
• Female
• Homozygote
• Humans
• Infant
• Male
• Mutation, Missense
• Pedigree
• Recombinant Proteins (genetics)
• Skin (pathology)