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Wide clinical spectrum in a family with hereditary lymphedema type I due to a novel missense mutation in VEGFR3.

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Spiegel, Ronen Ghalamkarpour, Arash [UCL] Daniel-Spiegel, Etty Vikkula, Miikka [UCL] Shalev, Stavit A

Hereditary lymphedema type I (HL-I), also known as Milroy disease, is an autosomal dominant disorder characterized by typical phenotype of infantile onset lower-limb lymphedema accompanied by variable expression of recurrent episodes of cellulites, toenail changes, and papillomatosis. Mutations in the vascular endothelial growth factor receptor 3 (VEGFR3), also known as FLT4 gene, which encodes a lymphatic endothelial-specific tyrosine kinase receptor, have been identified as a genetic cause of HL-I. We report a large Muslim Arab family residing in northern Israel with 14 individuals presenting clinical features of HL-I. Genetic analysis revealed novel missense mutation E1106K in the tyrosine kinase domain II of VEGFR3 that cosegregates with the disorder in the family. Most affected individuals presented with bilateral congenital lower-limb lymphedema. Wide intrafamilial phenotypic variability included two asymptomatic individuals, a case of prenatal hydrothorax evolving to hydrops fetalis, and a late-onset complication, yet unreported, of chronic degenerative joint disease of the knees. This report broadens the known "classic" phenotype of HL-I.

Document type Article de périodique (Journal article) – Journal Article, Research Support, Non-U.S. Gov't
Access type Accès restreint
Publication date 2006
Journal information "Journal of human genetics" - Vol. 51, no. 10, p. 846-50 (2006)
Peer reviewed yes
issn 1434-5161
Publication status Publié
Affiliation UCL - MD/BICL - Département de biochimie et de biologie cellulaire
MESH Subject Adolescent ; Adult ; Aged ; Child ; Family Health ; Female ; Humans ; Infant ; Infant, Newborn ; Lymphedema - congenital - diagnosis - genetics ; Male ; Middle Aged ; Mutation, Missense ; Pedigree ; Phenotype ; TYK2 Kinase - genetics ; Vascular Endothelial Growth Factor Receptor-3 - genetics
Links
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Bibliographic reference Spiegel, Ronen ; Ghalamkarpour, Arash ; Daniel-Spiegel, Etty ; Vikkula, Miikka ; Shalev, Stavit A. Wide clinical spectrum in a family with hereditary lymphedema type I due to a novel missense mutation in VEGFR3.. In: Journal of human genetics, Vol. 51, no. 10, p. 846-50 (2006)
Permanent URL http://hdl.handle.net/2078.1/27099