Abstrakt

Novel premature termination codon mutation in FBN1 gene in an infant with severe Marfan syndrome.

Brissia Lazalde, Gerardo Aguirre-Hernández, Rosa M. González-Arreola, José L Venegas Rodríguez, Antonio E Gonzalez Font

Marfan syndrome is a systemic disorder of connective tissue inherited in an autosomal dominant fashion due to mutations in the FBN1 gene. It is characterized by a broad clinical variability within and between families as well as in individuals. The clinical presentation in the early onset form of the disease is severe and rapidly progressive; deaths among infantile Marfan syndrome patients are associated with congestive heart failure due to severe mitral and/or tricuspid valvulopathy, although this severe presentation is rarely diagnosed and the majority of cases are sporadic. Here we report a case of an infant with severe cardiomyopathy diagnosed at 18 months of age. The clinical examination showed tall stature, dolichocephaly, long shaped facies, down slanting palpebral fissures, malar hypoplasia, high palate, protruding ears, pectus carinatum, scoliosis, articular hypermobility, long fingers and toes, hind foot deformity and myopia. A fibrillinopathy was suspected and molecular diagnostic tests of the TGFBR1, TGFBR2 and FBN1 genes were conducted. The direct analysis of the genes showed a heterozygous duplication of 4 nucleotides (c.5662_5665dupATGT) in FBN1 gene that creates a shift in the reading frame at codon 1889, producing a premature termination codon, 6 positions downstream (p.Cys1889Tyrfs*7). According to established criteria, it is a putative pathogenic mutation not reported previously. The mutation was not present in the parents. PTC mutations are commonly associated with milder phenotypes; therefore, this case highlights the complexity of the pathogenicity of FBN1 mutations. Molecular diagnosis in children suspected of having Marfan syndrome guarantees an early diagnosis, prognosis and timely therapy.