[Identification of VEGFR3 gene mutation in a Chinese family with autosomal dominant primary congenital lymphoedema].
OBJECTIVE
To identify the disease-causing gene in a four-generation Chinese family with 9 members affected with primary congenital lymphoedema (PCL, also known as Milroy disease).


METHODS
Linkage analysis was performed with a few microsatellite markers flanking the candidate genetic loci for PCL, including 3 known genes associated with autosomal dominant PCL. For mutation analysis, VEGFR3 gene was sequenced with DNA from the proband. Direct DNA sequencing of exon 25 of the VEGFR3 gene was performed in all family members.


RESULTS
The disease gene in the family was mapped to chromosome 5q35.3 with a maximum Lod score of 2.07. Direct DNA sequencing of VEGFR3 gene revealed a heterozygous C to T transition at nucleotide 3341, resulting in p.Pro1114Leu mutation. The p.Pro1114Leu mutation co-segregated with all affected individuals in the family.


CONCLUSIONS
This study identified a C3341T (p.Pro1114Leu) mutation in the VEGFR3 gene in a Chinese family with PCL, provided evidence that VEGFR3 mutation can cause PCL in Chinese.
Sheng
Ji-qun
JQ
Key Laboratory of Molecular Biophysics of Ministry of Education, College of Life Science and Technology, Center for Human Genome Research, Huazhong University of Science and Technology, Wuhan, Hubei, 430074 PR China.
Zeng
Feng
F
Li
Chang
C
Liu
Jing-yu
JY
Wang
Qing
Q
Liu
Mu-gen
MG
D019943:Amino Acid Substitution; D044466:Asian People / Q000235:genetics; D002386:Cataract / Q000235:genetics; D056426:Genetic Loci; D006801:Humans; D008126:Lod Score; D008209:Lymphedema / Q000235:genetics*; D018895:Microsatellite Repeats / Q000235:genetics*; D009154:Mutation; D017354:Point Mutation; D040321:Vascular Endothelial Growth Factor Receptor-3 / Q000235:genetics*
D040321:Vascular Endothelial Growth Factor Receptor-3