[Fibrillin-1 gene mutation in Chinese patients with Marfan syndrome and its gene diagnosis by haplotype analysis].
OBJECTIVE
To analyze fibrillin-1 (FBN(1)) gene mutation in Chinese patients with Marfan syndrome(MFS) and to make a gene diagnosis by haplotype analysis for MFS.


METHODS
Nine MFS families were analysed with single strand conformation polymorphism(SSCP) and DNA sequencing. With the use of four primers designed in the flanking sequences of each short-sequence tandem-repeat region in FBN(1) gene, the haplotype-segregation analysis for MFS(B) was performed.


RESULTS
In MFS(A)II(1), PCR-SSCP detected SSCP band alterations in exon 25 of FBN(1) gene; direct sequencing showed a small 13bp deletion, the deleted sequence being gcctctgcaccca at base 3243-3456 of cDNA. This mutation caused a frame-shift which was never seen in any unaffected members of the family, and it was a heterozygous mutation; neither of them was identified in 100 chromosomes from 50 normal control individuals. Haplotype-segregation analysis suggested that the disease was passed from Subject I(2) to Subject II(2), Subject II(3), Subject II(5) with the same allele in MFS B family, the proband's daughter also inherited the allele. These data indicated that MFS(B) family was linked to FBN(1) gene, the proband's daughter was an asymptomatic patient.


CONCLUSIONS
The combination of mutation analysis and haplotype analysis can provide more evidence for gene diagnosis.
Wang
Bing
B
Department of Surgery, the Second Affiliated Xiangya Hospital, Central South University, Changsha, Hunan, PR China. mimiwb@public.cs.hn.cn
Hu
Dong-xu
DX
Xia
Jia-hui
JH
Li
Qi
Q
Lu
Guo-hua
GH
D001483:Base Sequence; D002681:China; D004247:DNA / Q000737:chemistry / Q000235:genetics; D004252:DNA Mutational Analysis; D005192:Family Health; D005260:Female; D000071838:Fibrillin-1; D000071837:Fibrillins; D006239:Haplotypes / Q000235:genetics*; D006801:Humans; D008297:Male; D008382:Marfan Syndrome / Q000175:diagnosis / Q000235:genetics*; D008840:Microfilament Proteins / Q000235:genetics*; D009154:Mutation; D010375:Pedigree; D012150:Polymorphism, Restriction Fragment Length; D018807:Polymorphism, Single-Stranded Conformational; D017384:Sequence Deletion; D054392:Adipokines
D004247:DNA; D000071838:Fibrillin-1; D000071837:Fibrillins; D008840:Microfilament Proteins; C000605722:FBN1 protein, human; D054392:Adipokines