title: An FBN1 pseudoexon mutation in a patient with Marfan syndrome: confirmation of cryptic mutations leading to disease.
abstract: Marfan syndrome (MFS) results from heterozygous mutations in FBN1. However, genetic analyses of deoxyribonucleic acid (DNA) from approximately 10-30% of MFS patients who meet diagnostic criteria do not reveal an identifiable FBN1 mutation. In a patient who met the diagnostic criteria for MFS, bidirectional DNA sequencing of exons and intron-exon boundaries of FBN1 failed to reveal a mutation. Assessment of the FBN1 message in dermal fibroblasts from the patient revealed insertion of a pseudoexon between exons 63 and 64. Sequencing of intron 63 identified a point mutation, IVS63+373, located near the middle of intron 63 of FBN1 that created a donor splice site in intron 63, leading to inclusion of a 93-bp fragment of intronic sequence in the FBN1 message. Identification of a novel pseudoexon mutation in FBN1, in association with a clinical diagnosis of MFS, confirms that cryptic mutations that are missed by the current DNA-based diagnostic methods have a causative role.
authors.affiliation: The Department of Internal Medicine, The University of Texas Medical School at Houston, 6431 Fannin, MSB 6.100, Houston, TX, 77030, USA.
authors.forename: Dong-Chuan
authors.initials: DC
authors.lastname: Guo
authors.affiliation: The Department of Internal Medicine, The University of Texas Medical School at Houston, 6431 Fannin, MSB 6.100, Houston, TX, 77030, USA.
authors.forename: Prateek
authors.initials: P
authors.lastname: Gupta
authors.affiliation: The Department of Internal Medicine, The University of Texas Medical School at Houston, 6431 Fannin, MSB 6.100, Houston, TX, 77030, USA.
authors.forename: Van
authors.initials: V
authors.lastname: Tran-Fadulu
authors.affiliation: The Department of Internal Medicine, The University of Texas Medical School at Houston, 6431 Fannin, MSB 6.100, Houston, TX, 77030, USA.
authors.forename: Tera V
authors.initials: TV
authors.lastname: Guidry
authors.affiliation: The Department of Internal Medicine, The University of Texas Medical School at Houston, 6431 Fannin, MSB 6.100, Houston, TX, 77030, USA.
authors.forename: Magalie S
authors.initials: MS
authors.lastname: Leduc
authors.affiliation: Center for Genetic Testing at Saint Francis, Tulsa, OK, USA.
authors.forename: Frederick V
authors.initials: FV
authors.lastname: Schaefer
authors.affiliation: The Department of Internal Medicine, The University of Texas Medical School at Houston, 6431 Fannin, MSB 6.100, Houston, TX, 77030, USA. Dianna.M.Milewicz@uth.tmc.edu.
authors.forename: Dianna M
authors.initials: DM
authors.lastname: Milewicz
mesh_terms: D000328:Adult; D001483:Base Sequence; D002648:Child; D004252:DNA Mutational Analysis / Q000379:methods; D005091:Exons / Q000235:genetics*; D005260:Female; D000071838:Fibrillin-1; D000071837:Fibrillins; D020022:Genetic Predisposition to Disease; D006801:Humans; D007438:Introns / Q000235:genetics; D008297:Male; D008382:Marfan Syndrome / Q000235:genetics*; D008840:Microfilament Proteins / Q000235:genetics*; D008875:Middle Aged; D008969:Molecular Sequence Data; D009154:Mutation / Q000235:genetics*; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D054392:Adipokines
chemical_list: D000071838:Fibrillin-1; D000071837:Fibrillins; D008840:Microfilament Proteins; D012333:RNA, Messenger; C000605722:FBN1 protein, human; D054392:Adipokines
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