Identification of a Novel VEGFR-3 Missense Mutation in a Chinese Family with Hereditary Lymphedema Type I

Zhengya Yu; Jingjing Wang; Shuling Peng; Bing Dong; Yang Li

doi:10.1016/S1673-8527(07)60097-6

Volume 34 Issue 10

Oct. 2007

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Identification of a Novel VEGFR-3 Missense Mutation in a Chinese Family with Hereditary Lymphedema Type I

doi: 10.1016/S1673-8527(07)60097-6

a
Department of General and Vascular Surgery, Beijing Tongren Hospital, Capital Medical University, Beijing 100730 China
b
Beijing Institute of Ophthalmology, Beijing Tongren Hospital, Capital Medical University, Beijing 100730 China

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Corresponding author: E-mail address: yangli64@hotmail.com (Yang Li)
Received Date: 2007-02-13
Accepted Date: 2007-03-19

Available Online: 2007-10-16

Publish Date: 2007-10-20

Abstract

Abstract

A novel mutation of vascular endothelial growth factor receptor gene (VEGFR-3), was identified in a four-generation Chinese family with hereditary lymphedema type I (HL-I). Genetic linkage analysis was performed on the known genetic locus for HL-I with a panel of polymorphic markers, and then mutations were screened out by direct sequencing. By genotyping, the family showed the linkage to HL-I locus on 5q35.3. Mutation screening analysis of the exons encoding the intracellular kinase domains of VEGFR-3, revealed a novel missense mutation D1055V. This mutation cosegregated with the disease phenotype in the family and was not found in 100 normal controls. This finding has expanded the spectrum of the VEGFR-3 gene mutations causing HL-I, and will be useful for further genetic consultation and genetic diagnosis.
- hereditary lymphedema,
- missense mutation,
- autosomal dominant

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References(20)

References

[1]	Brice, G, Child, et al. Milroy disease and the VEGFR-3 mutation phenotype J Med Genet, 42 (2005),pp. 98-102
[2]	Dale, RF The inheritance of primary lymphoedema J Med Genet, 22 (1985),pp. 274-278
[3]	Gregl, A, von Heyden, et al. [Primary lymphedema] Z Lymphol, 7 (1983),pp. 21-28
[4]	Evans, AL, Brice, et al. Mapping of primary congenital lymphedema to the 5q35.3 region Am J Hum Genet, 64 (1999),pp. 547-555
[5]	Ferrell, RE, Levinson, et al. Hereditary lymphedema: evidence for linkage and genetic heterogeneity Hum Mol Genet, 7 (1998),pp. 2073-2078
[6]	Irrthum, A, Karkkainen, et al. Congenital hereditary lymphedema caused by a mutation that inactivates VEGFR3 tyrosine kinase Am J Hum Genet, 67 (2000),pp. 295-301
[7]	Karkkainen, MJ, Ferrell, et al. Missense mutations interfere with VEGFR-3 signalling in primary lymphoedema Nat Genet, 25 (2000),pp. 153-159
[8]	Kaipainen, A, Korhonen, et al. Expression of the fms-like tyrosine kinase 4 gene becomes restricted to lymphatic endothelium during development Proc Natl Acad Sci USA, 92 (1995),pp. 3566-3570
[9]	Dumont, DJ, Jussila, et al. Cardiovascular failure in mouse embryos deficient in VEGF receptor-3 Science, 282 (1998),pp. 946-949
[10]	Evans, AL, Bell, et al. J Med Genet, 40 (2003),pp. 697-703
[11]	Ghalamkarpour, A, Morlot, et al. Clin Genet, 70 (2006),pp. 330-335
[12]	Spiegel, R, Ghalamkarpour, et al. J Hum Genet, 51 (2006),pp. 846-850
[13]	Wang, Q, Shen, et al. Cell, 80 (1995),pp. 805-811
[14]	Wang, Q, Curran, et al. Nat Genet, 12 (1996),pp. 17-23
[15]	Aprelikova, O, Pajusola, et al. FLT4, a novel class III receptor tyrosine kinase in chromosome 5q33-qter Cancer Res, 52 (1992),pp. 746-748
[16]	Galland, F, Karamysheva, et al. Chromosomal localization of FLT4, a novel receptor-type tyrosine kinase gene Genomics, 13 (1992),pp. 475-478
[17]	Iljin, K, Karkkainen, et al. FASEB J, 15 (2001),pp. 1028-1036
[18]	McTigue, MA, Wickersham, et al. Crystal structure of the kinase domain of human vascular endothelial growth factor receptor 2: a key enzyme in angiogenesis Structure, 7 (1999),pp. 319-330
[19]	Hubbard, SR Crystal structure of the activated insulin receptor tyrosine kinase in complex with peptide substrate and ATP analog EMBO J, 16 (1997),pp. 5572-5581
[20]	Albert, B, Johnson, et al.