MOLECULAR-CLONING OF THE MICROFIBRILLAR PROTEIN MFAP3 AND ASSIGNMENT OF THE GENE TO HUMAN-CHROMOSOME 5Q32-Q33.2
Authors: ABRAMS, WR; MA, RI; KUCICH, U; BASHIR, MM; DECKER, S; TSIPOURAS, P; MCPHERSON, JD; WASMUTH, JJ; ROSENBLOOM, J
Microfibrils having a diameter of 10-12 nm, found either in association with elastin or independently, are an important component of the extracellular matrix of many tissues, but characterization of these microfibrils is incomplete. To further our understanding of the gene structure of proteins composing the microfibrils and to identify their chromosomal location, we have cloned and characterized another microfibril protein, designated microfibril-associated protein-3 (MFAP3). The human gene encoding MFAP3 has a very simple structure, containing only two translated exons encoding a protein of 362 amino acids. Monospecific antibodies prepared against the recombinantly expressed protein reacted with the microfibrils found in ocular zonules. MFAP3 does not appear to share homology with any other known protein. The gene was found to be located on chromosome 5q32-q33.2, near the locus 5q21-q31 reported for the fibrillin gene, FBN2, which has been linked to congenital contractural arachnodactyly. MFAP3 is a candidate gene for heritable diseases affecting microfibrils. (C) 1995 Academic Press, Inc.
Comprehensive Clinical and Molecular Assessment of 32 Probands With Congenital Contractural Arachnodactyly: Report of 14 Novel Mutations and Review of the Literature
Authors: Callewaert, Bert L.; Loeys, Bart L.; Ficcadenti, Anna; Vermeer, Sascha; Landgren, Magnus; Kroes, Hester Y.; Yaron, Yuval; Pope, Michael; Foulds, Nicola; Boute, Odile; Galan, Francisco; Kingston, Helen; Van der Aa, Nathalie; Salcedo, Iratxe; Swinkels, Marielle E.; Wallgren-Pettersson, Carina; Gabrielli, Orazio; De Backer, Julie; Coucke, Paul J.; De Paepe, Anne M.
Beals-Hecht syndrome or congenital contractural arachnodactyly (CCA) is a rare, autosomal dominant connective tissue disorder characterized by crumpled ears, arachnodactyly, contractures, and scoliosis. Recent reports also mention aortic root dilatation, a finding previously thought to differentiate the condition from Marfan syndrome (MFS). In many cases, the condition is caused by mutations in the fibrillin 2 gene (FBN2) with 26 mutations reported so far, all located in the middle region of the gene (exons 23-34). We directly sequenced the entire FBN2 gene in 32 probands clinically diagnosed with CCA. In 14 probands, we found 13 new and one previously described FBN2 mutation including a mutation in exon 17, expanding the region in which FBN2 mutations occur in CCA. Review of the literature showed that the phenotype of the FBN2 positive patients was comparable to all previously published FBN2-positive patients. In our FBN2-positive patients, cardiovascular involvement included mitral valve prolapse in two adult patients and aortic root enlargement in three patients. Whereas the dilatation regressed in one proband, it remained marked in a child proband (z-score: 4.09) and his father (z-score: 2.94), warranting echocardiographic follow-up. We confirm paradoxical patellar laxity and report keratoconus, shoulder muscle hypoplasia, and pyeloureteral junction stenosis as new features. In addition, we illustrate large intrafamilial variability. Finally, the FBN2-negative patients in this cohort were clinically indistinguishable from all published FBN2-positive patients harboring a FBN2 mutation, suggesting locus heterogeneity. Hum Mutat 30, 334-341, 2009. (C) 2008 Wiley-Liss, Inc.