RESUMEN
AIM: To characterize the disease-causing mutations in a Chinese family with ectopia lentis syndrome (ELS). METHODS: Patients and their family members were given complete physical, ophthalmic, and cardiovascular examinations. Genomic DNA samples were extracted from the peripheral blood of the pedigree members and 100 healthy controls. Mutation screening was performed in the fibrillin-1 (FBN1) gene by bi-directional sequencing of the amplified products. The mutation was analyzed using two bioinformatics methods. RESULTS: A novel heterozygous c.305G>A mutation in exon 3 of FBN1 was detected. As a result of this change, a highly conserved cysteine residue was replaced by a tyrosine residue (p.C102Y). Another mutation was found in the same exon (c.303T>C), which did not change the amino acid sequence. Both mutations were discovered in each affected individual, but not in the unaffected family members, or in 100 ethnically matched controls. A bioinformatics analysis predicted that mutation p.C102Y would affect protein function. CONCLUSION: In the first epidermal growth factor-like module, we identified a novel FBN1 mutation (p.C102Y), which caused ELS in the family. Our study presented a unique phenotype, including some distinct ophthalmic findings, such as hypoplasia of the iris and anisometropia. Our results expanded the mutation spectrum of FBN1 and enriched the overall knowledge of genotype-phenotype correlations due to FBN1 mutations.
RESUMEN
Marfan syndrome is an autosomal dominant disorder of connective tissue caused by mutations in the gene encoding fibrillin-1 (FBN1), a matrix component of microfibrils. Dural ectasia, i.e. enlargement of the neural canal mainly located in the lower lumbar and sacral region, frequently occurs in Marfan patients. The aim of our study was to investigate the role of dural ectasia in raising the diagnosis of Marfan syndrome and its association with FBN1 mutations. We studied 40 unrelated patients suspected for MFS, who underwent magnetic resonance imaging searching for dural ectasia. In all of them FBN1 gene analysis was also performed. Thirty-seven patients resulted affected by Marfan syndrome according to the '96 Ghent criteria; in 30 of them the diagnosis was confirmed when revaluated by the recently revised criteria (2010). Thirty-six patients resulted positive for dural ectasia. The degree of dural ectasia was grade 1 in 19 patients, grade 2 in 11 patients, and grade 3 in 6 patients. In 7 (24%) patients, the presence of dural ectasia allowed to reach a positive score for systemic feature criterion. Twenty-four patients carried an FBN1 mutation, that were represented by 13 missense (54%), and 11 (46%) mutations generating a premature termination codon (PTC, frameshifts and stop codons). No mutation was detected in the remaining 16 (6 patients with MFS and 10 with related disorders according to revised Ghent criteria). The prevalence of severe (grade 2 and grade 3) involvement of dura mater was higher in patients harbouring premature termination codon (PTC) mutations than those carrying missense-mutations (8/11 vs 2/13, P = 0.0111). Our data emphasizes the importance of dural ectasia screening to reach the diagnosis of Marfan syndrome especially when it is uncertain and indicates an association between PTC mutations and severe dural ectasia in Marfan patients.