Prenatal diagnosis and a donor splice site mutation in fibrillin in a family with Marfan syndrome.
The Marfan syndrome, an autosomal dominant connective tissue disorder, is manifested by abnormalities in the cardiovascular, skeletal, and ocular systems. Recently, fibrillin, an elastin-associated microfibrillar glycoprotein, has been linked to the Marfan syndrome, and fibrillin mutations in affected individuals have been documented. In this study, genetic linkage analysis with fibrillin specific markers was used to establish the prenatal diagnosis in an 11-wk-gestation fetus in a four-generation Marfan kindred. At birth, skeletal changes suggestive of the Marfan syndrome were observed. Reverse transcription-PCR amplification of the fibrillin gene mRNA detected a deletion of 123 bp in one allele in affected relatives. This deletion corresponds to an exon encoding an epidermal growth factor-like motif. Examination of genomic DNA showed a G-->C transversion at the +1 consensus donor splice site.
Godfrey
M
M
Department of Pediatrics, University of Nebraska Medical Center, Omaha 68198.
Vandemark
N
N
Wang
M
M
Velinov
M
M
Wargowski
D
D
Tsipouras
P
P
Han
J
J
Becker
J
J
Robertson
W
W
Droste
S
S
D000328:Adult; D001483:Base Sequence; D015139:Blotting, Southern; D004252:DNA Mutational Analysis; D015252:Deoxyribonucleases, Type II Site-Specific; D004815:Epidermal Growth Factor / Q000235:genetics; D005091:Exons; D005260:Female; D000071837:Fibrillins; D006801:Humans; D008382:Marfan Syndrome / Q000175:diagnosis* / Q000235:genetics*; D008840:Microfilament Proteins / Q000235:genetics*; D008969:Molecular Sequence Data; D010375:Pedigree; D017354:Point Mutation; D016133:Polymerase Chain Reaction; D012150:Polymorphism, Restriction Fragment Length; D011247:Pregnancy; D011296:Prenatal Diagnosis; D012326:RNA Splicing; D012091:Repetitive Sequences, Nucleic Acid; D017423:Sequence Analysis, RNA
D000071837:Fibrillins; D008840:Microfilament Proteins; D004815:Epidermal Growth Factor; D015252:Deoxyribonucleases, Type II Site-Specific; C027046:TCGA-specific type II deoxyribonucleases