Genotype-Phenotype Correlation in Children: The Impact of FBN1 Variants on Pediatric Marfan Care.

Genes
Veronika C StarkThomas S Mir

Abstract

Currently, no reliable genotype-phenotype correlation is available for pediatric Marfan patients in everyday clinical practice. We investigated correlations of FBN1 variants with the prevalence and age of onset of Marfan manifestations in childhood and differentiated three groups: missense/in-frame, splice, and nonsense/frameshift variants. In addition, we differentiated missense variants destroying or generating a cysteine (cys-missense) and alterations not affecting cysteine. We categorized 105 FBN1-positive pediatric patients. Patients with cys-missense more frequently developed aortic dilatation (p = 0.03) requiring medication (p = 0.003), tricuspid valve prolapse (p = 0.03), and earlier onset of myopia (p = 0.02) than those with other missense variants. Missense variants correlated with a higher prevalence of ectopia lentis (p = 0.002) and earlier onset of pulmonary artery dilatation (p = 0.03) than nonsense/frameshift, and dural ectasia was more common in the latter (p = 0.005). Pectus excavatum (p = 0.007) appeared more often in patients with splice compared with missense/in-frame variants, while hernia (p = 0.04) appeared earlier in the latter. Findings on genotype-phenotype correlations in Marfan-affected children can ...Continue Reading

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Methods Mentioned

BETA
PCR
Illumina sequencing
dissection

Software Mentioned

Sequence Pilot
GraphPad
SPSS
GraphPad Prism
Excel
SeqPatient
Human Splicing Finder
Filemaker
varSEAK
SeqNext

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