Our study reports a novel mutation in FBN1 in a Chinese family and to diagnose this family as Marfan syndrome, we also expand the genotype-phenotype correlation of this disease.
However, in the same pedigree, phenotypic variances are observed despite the inheritance of the identical mutated null allele, including Fibrillin1 (FBN1), which is responsible for development of the haploinsufficient Marfan disease.
Our data from the quantitation of FBN1 transcripts provide support for the hypothesis that mutations causing premature stop codons result in a milder phenotype than classical MFS by reducing the stability of the mutant transcript and, consequently, decreasing the interference of mutant polypeptide in the formation of fibrillin fibers.
Twenty patients could be classified as ID with other extra-skeletal features of the Marfan syndrome (MFS) spectrum: 4 pathogenic FBN1 mutations and 4 chromosomal imbalances were found (2 patients with both FBN1 mutation and chromosomal rearrangement) (29%).
Among 29 non-definite MFS probands, 1 (3%) FBN1, 2 (7%) TGFBR1, and 3 (10%) TGFBR2 mutations were found, and 4 ACTA2 mutations were found in the 23 probands examined without FBN1, TGFBR1, or TGFBR2 mutations.
The aim of this study was to explore whether there are regional and sex differences in the thoracic aorta function of mice heterozygous for the fibrillin 1 (<i>Fbn1</i>) allele encoding a missense mutation (<i>Fbn1</i><sup>C1039G/+</sup>), the most common class of mutation in MFS.
Taken together, these data suggest that fibrillin-1 contributes to cardiac reserve in the face of hemodynamic stress, critically implicate nonmyocytes in disease pathogenesis, and validate ERK as a therapeutic target in MFS-related cardiac decompensation.
Here, we report a newborn with severe Marfan syndrome and a novel mutation involving cysteine substitution within one of the epidermal growth factor-like domains of FBN1.
It has been reported that the severe phenotypes of infantile MFS correlate with mutations in the mid region of FBN1, however, mutations were not detected in this region in the population analyzed in this study.
In this work, we report 12 FBN1 mutations identified by temperature-gradient gel electrophoresis screening of exons 24-40 in 127 individuals with Marfan syndrome or related disorders.
It was long believed that a structural impairment formed the basis of Marfan syndrome as deficiency in the structural extracellular matrix component, fibrillin-1 is the cause of Marfan syndrome.
Studies of MFS and CCA mice have correlated the skeletal phenotypes of these mutant animals with distinct pathophysiological mechanisms that reflect the contextual contribution of fibrillin-1 and -2 scaffolds to TGFβ and BMP signaling during bone patterning, growth and metabolism.
We conclude that complete loss of one FBN1 allele does not predict a mild phenotype, and these findings support the hypothesis that true haploinsufficiency can lead to the classical phenotype of Marfan syndrome.
Fibrillin-1 (FBN-1) is the disease gene for Marfan's syndrome and an FBN-1 polymorphism has been associated with large artery stiffening and elevated pulse pressure (PP) in patients with cardiovascular disease.