Laboratory for Molecular Diagnostics
Center for Nephrology and Metabolic Disorders

Vascular endothelial growth factor receptor 3

The FLT4 gene encodes a tyrosin kinase receptor which binds endothelial growth factor D and C. Mutations are found in autosomal dominant hereditary lymphedema type 1a and in tumor cells of capillary infantile hemangiomas.

Genetests:

Clinic Method Carrier testing
Turnaround 5
Specimen type genomic DNA
Research Method Genomic sequencing of the entire coding region
Turnaround 25
Specimen type genomic DNA
Clinic Method Massive parallel sequencing
Turnaround 25
Specimen type genomic DNA

Related Diseases:

Capillary infantile hemangioma
FLT4
Hereditary lymphedema type 1a
FLT4

References:

1.

Warrington JA et. al. (1992) A radiation hybrid map of 18 growth factor, growth factor receptor, hormone receptor, or neurotransmitter receptor genes on the distal region of the long arm of chromosome 5.

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2.

Aprelikova O et. al. (1992) FLT4, a novel class III receptor tyrosine kinase in chromosome 5q33-qter.

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3.

Galland F et. al. (1992) Chromosomal localization of FLT4, a novel receptor-type tyrosine kinase gene.

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4.

Pajusola K et. al. (1992) FLT4 receptor tyrosine kinase contains seven immunoglobulin-like loops and is expressed in multiple human tissues and cell lines.

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5.

Kaipainen A et. al. (1995) Expression of the fms-like tyrosine kinase 4 gene becomes restricted to lymphatic endothelium during development.

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6.

Pajusola K et. al. (1994) Signalling properties of FLT4, a proteolytically processed receptor tyrosine kinase related to two VEGF receptors.

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7.

Offori TW et. al. (1993) Angiosarcoma in congenital hereditary lymphoedema (Milroy's disease)--diagnostic beacons and a review of the literature.

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8.

Lee J et al. (1996) Vascular endothelial growth factor-related protein: a ligand and specific activator of the tyrosine kinase receptor Flt4.

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9.

Dumont DJ et. al. (1998) Cardiovascular failure in mouse embryos deficient in VEGF receptor-3.

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10.

Ferrell RE et. al. (1998) Hereditary lymphedema: evidence for linkage and genetic heterogeneity.

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11.

Karkkainen MJ et. al. (2000) Missense mutations interfere with VEGFR-3 signalling in primary lymphoedema.

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12.

Irrthum A et. al. (2000) Congenital hereditary lymphedema caused by a mutation that inactivates VEGFR3 tyrosine kinase.

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13.

Karkkainen MJ et. al. (2001) A model for gene therapy of human hereditary lymphedema.

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14.

Walter JW et. al. (2002) Somatic mutation of vascular endothelial growth factor receptors in juvenile hemangioma.

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15.

Evans AL et. al. (2003) Identification of eight novel VEGFR-3 mutations in families with primary congenital lymphoedema.

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16.

Kim H et. al. (2003) Molecular mechanisms in lymphangiogenesis: model systems and implications in human disease.

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17.

Cursiefen C et. al. (2006) Nonvascular VEGF receptor 3 expression by corneal epithelium maintains avascularity and vision.

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18.

Spiegel R et. al. (2006) Wide clinical spectrum in a family with hereditary lymphedema type I due to a novel missense mutation in VEGFR3.

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19.

Ghalamkarpour A et. al. (2006) Hereditary lymphedema type I associated with VEGFR3 mutation: the first de novo case and atypical presentations.

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20.

Siekmann AF et. al. (2007) Notch signalling limits angiogenic cell behaviour in developing zebrafish arteries.

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21.

Tammela T et. al. (2008) Blocking VEGFR-3 suppresses angiogenic sprouting and vascular network formation.

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22.

Connell FC et. al. (2009) Analysis of the coding regions of VEGFR3 and VEGFC in Milroy disease and other primary lymphoedemas.

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23.

Ghalamkarpour A et. al. (2009) Recessive primary congenital lymphoedema caused by a VEGFR3 mutation.

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24.

Wang Y et. al. (2010) Ephrin-B2 controls VEGF-induced angiogenesis and lymphangiogenesis.

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25.

Benedito R et. al. (2012) Notch-dependent VEGFR3 upregulation allows angiogenesis without VEGF-VEGFR2 signalling.

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26.

Zhang Y et. al. (2014) Activation of vascular endothelial growth factor receptor-3 in macrophages restrains TLR4-NF-κB signaling and protects against endotoxin shock.

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Update: Sept. 26, 2018