Fibrillin‐1 (FBN1) gene frameshift mutations in Marfan patients: genotype–phenotype correlation
Adult
Male
0301 basic medicine
Genotype
Fibrillin-1
610
MASS
Fibrillins
Marfan Syndrome
03 medical and health sciences
Frameshift mutation
Settore BIO/13 - BIOLOGIA APPLICATA
Humans
Mass Screening
RNA, Messenger
Frameshift Mutation
Fibrilin-1 gene
0303 health sciences
Aortic aneurysm
Polymorphism, Genetic
Microfilament Proteins
DNA
Exons
Aortic aneurysm; Fibrilin-1 gene; Frameshift mutations; Marfan syndrome; MASS
3. Good health
Marfan syndrome
Mutagenesis, Insertional
Phenotype
Female
DOI:
10.1034/j.1399-0004.2001.590610.x
Publication Date:
2003-03-11T11:26:35Z
AUTHORS (12)
ABSTRACT
Marfan syndrome (MFS) is a multisystemic disease associated with mutations in the fibrillin‐1 gene. Most of the reported mutations are missense substitutions mainly affecting the epidermal growth factor (EGF)‐like protein domain structure and the calcium‐binding (cb) site. The aim of our study was to investigate the correlation between fibrillin‐1 frameshift mutations and the clinical phenotype in patients affected by MFS. In 48 out of 66 Marfan patients a pathogenetic mutation was found. We detected novel mutations causing premature termination codon in exons 19, 37, 40 and 41 of four Italian patients. The first mutation in exon 19 (cbEGF #8 domain) results in a clinical phenotype involving mainly the skeletal and cardiovascular systems. Interestingly, we noticed that, while mutations in exons 37 and 41 (eight cysteine domains #4 and #5) are milder, the mutation in exon 40 (cbEGF #24 domain) is more severe and causes major cardiovascular involvement with thoracic and abdominal aortic aneurysms. It is noteworthy that the degree of the severity in the phenotype of one of our patients and another from the literature carrying a mutation in exon 41 could be explained with alterations in mRNA expression.
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