[Mutation analysis and prenatal diagnosis of FBN1 gene mutations for four patients with Marfan syndrome].
OBJECTIVE
To screen for mutations of fibrillin-1 (FBN1) gene in 4 patients with Marfan syndrome in order to provide prenatal diagnosis and genetic counseling.


METHODS
Potential mutations of the FBN1 gene in the probands were detected with PCR and DNA sequencing. Subsequently, genomic DNA was extracted from amniotic fluid sampled between 18 to 20 weeks gestation. The mutations were confirmed with denaturing high-performance liquid chromatography - robust microsatellite instability (DHPLC-MSI) analysis with maternal DNA as reference. The products were further analyzed by direct sequencing and BLAST search of NCBI database.


RESULTS
An IVS46+1G>A substitution was identified in patient A at +1 position of intron 46 of the FBN1 gene. Two novel missense mutations were respectively discovered at positions +4453 of intron 35 in patient B (Cys1485Gly) and position +2585 of intron 21 in patient C (Cys862Tyr). In patient D, a novel deletion (c.3536 delA) was found at position +3536 of intron 28. In all of the 4 cases, the same mutations have been identified in the fetuses.


CONCLUSIONS
FBN1 gene analysis can provide accurate diagnosis of Marfan syndrome, which can facilitate both prenatal diagnosis and genetic counseling.
Department of Cardiac Surgery, Anzhen Hospital, Capital Medical University, Beijing 100029, P. R. China. Email: shoe666@hotmail.com.
Shi-qiu
SQ
Song
Bao-jian
BJ
Zhao
Shuang
S
Li
Jian-qun
JQ
Zhang
Hui
H
Wang
Chan-wei
CW
Jia
Feng-huan
FH
Zhang
Xu
X
Zhang
Jin-sheng
JS
Xie
D000328:Adult; D001483:Base Sequence; D004252:DNA Mutational Analysis; D005260:Female; D000071838:Fibrillin-1; D000071837:Fibrillins; D006801:Humans; D007438:Introns; D008297:Male; D008382:Marfan Syndrome / Q000175:diagnosis / Q000196:embryology* / Q000235:genetics*; D008840:Microfilament Proteins / Q000235:genetics*; D008969:Molecular Sequence Data; D020125:Mutation, Missense; D011247:Pregnancy; D011296:Prenatal Diagnosis; D017384:Sequence Deletion; D054392:Adipokines
D000071838:Fibrillin-1; D000071837:Fibrillins; D008840:Microfilament Proteins; C000605722:FBN1 protein, human; D054392:Adipokines