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Two rare missense mutations in the fibrillin?1 gene associated with atypical cardiovascular manifestations in a Chinese patient affected by Marfan syndrome.

ABSTRACT: The present report aimed to evaluate the results of screen mutations of the fibrillin (FBN) 1 gene and analyze the symptoms in one Chinese patient clinically diagnosed with Marfan syndrome (MFS). Clinical data were collected and FBN1 gene sequencing was performed. Genomic DNA was extracted from the blood sample of the patient. All 65 exons were screened using a polymerase chain reaction assay. The diagnosis of MFS was confirmed via identification of symptoms presenting in the skeletal system (arachnodactyly, walker wrist and thumb signs) and the ocular system (ectopia lentis), in addition to a positive family history. The patient's cardiovascular manifestations (dilatation of the four cardiac chambers, severe mitral valve regurgitation and a large saccular aneurysm of the non?coronary sinus of Valsalva) were atypical to those that most frequently occur in cases of MFS. Following gene sequencing, two novel heterozygous mutations of the FBN?1 gene were identified: c.3442C>G in exon 27, proline replaced with alanine (p. Pro1148Ala) and c.6388G>A in exon 52, glutamic acid replaced with lysine (p. Glu2130Lys). The clinical symptoms and family history were important in the diagnosis of MFS, however the atypical signs that presented in the cardiovascular system may be associated with the disease, and may be noted for further cases in the future. Gene sequencing further verified the correct diagnosis of MFS.

SUBMITTER: Zhang M

PROVIDER: S-EPMC6059719 | biostudies-literature | 2018 Jul

REPOSITORIES: biostudies-literature

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Two rare missense mutations in the fibrillin‑1 gene associated with atypical cardiovascular manifestations in a Chinese patient affected by Marfan syndrome.

Zhang Miao M Zhou Yaqi Y Peng Yang Y Jin Lijun L

Molecular medicine reports 20180522 1

The present report aimed to evaluate the results of screen mutations of the fibrillin (FBN) 1 gene and analyze the symptoms in one Chinese patient clinically diagnosed with Marfan syndrome (MFS). Clinical data were collected and FBN1 gene sequencing was performed. Genomic DNA was extracted from the blood sample of the patient. All 65 exons were screened using a polymerase chain reaction assay. The diagnosis of MFS was confirmed via identification of symptoms presenting in the skeletal system (ar ...[more]

PMID: 29845260

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Project description:BackgroundMarfan syndrome (MFS) is a heritable disorder of connective tissue resulting from pathogenic variants of the fibrillin-1 gene (FBN1). Neonatal Marfan syndrome (nMFS) is rare and the most severe form of MFS, involving rapidly progressive cardiovascular dysfunction leading to death during early childhood. The constant enrichment of the nMFS mutation spectrum is helpful to improve our understanding of genotype-phenotype correlations in the disease. Herein, we report a novel dominant mutation in exon 26 of FBN1 (c.3331 T > C) in a sporadic case with nMFS.Case presentationAn 8-month-old Han Chinese girl presented with the classic nMFS phenotype, including prominent manifestations of bone overgrowth, aortic root dilatation, and multiple cardiac valve dysfunctions. Genetic analysis revealed that she was heterozygous for a de novo FBN1 missense mutation (c.3331 T > C). The mutation leads to the substitution of a highly conserved FBN1 cysteine residue (p.Cys1111Arg), which is likely to severely perturb the FBN1 structure because of an alteration of the disulfide bond pattern in the calcium-binding epidermal growth factor-like (cbEGF) 12 domain. This variant was absent in 208 ethnically matched controls, providing further evidence that it may be causative of nMFS. An analysis of nMFS-associated mutations from the UMD-FBN1 database indicates that those de novo mutations altering disulfide bonds or Ca(2+) binding sites of the cbEGF domains encoded by exons 25-33, and a lack of phenotypic heterogeneity may be associated with an increased risk for nMFS.ConclusionWe diagnosed an infant with rare nMFS showing rapidly progressive cardiovascular dysfunction and widely systemic features. As the only causal FBN1 mutation identified in the patient, the missense mutation c.3331 T > C (p.Cys1111Arg) was associated with the severe phenotype of MFS. However, the pathogenicity of the novel mutation needs further confirmation in other patients with nMFS. Our review of the prominent characteristics of nMFS mutations relative to classic or incomplete MFS-related mutations will be helpful for the recognition of novel nMFS-associated variants.

Dataset Information

Two rare missense mutations in the fibrillin?1 gene associated with atypical cardiovascular manifestations in a Chinese patient affected by Marfan syndrome.

Publications

Two rare missense mutations in the fibrillin‑1 gene associated with atypical cardiovascular manifestations in a Chinese patient affected by Marfan syndrome.

Similar Datasets

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