Recessive primary congenital lymphoedema caused by a VEGFR3 mutation.
J Med Genet
; 46(6): 399-404, 2009 Jun.
Article
en En
| MEDLINE
| ID: mdl-19289394
ABSTRACT
BACKGROUND:
Heterozygous mutations in VEGFR3 have been identified in some familial cases with dominantly inherited primary congenital lymphoedema, known as Nonne-Milroy disease. Recessive cases of primary lymphoedema with a genetic cause are not known, except for two families with syndromic hypotrichosis-lymphoedema-telangiectasia, with a SOX18 mutation. METHODS ANDRESULTS:
In this study, we present the first case of isolated primary congenital lymphoedema with recessive inheritance, caused by a homozygous mutation in VEGFR3. The novel mutation is a transition from alanine-to-threonine in amino acid 855, located in the ATP binding domain of the VEGFR3 receptor. Assessment of receptor function showed impaired ligand induced internalisation and ERK1/2 activity. Moreover, receptor phosphorylation was reduced, although less so than for a kinase-dead VEGFR3 mutation, which causes Nonne-Milroy disease.CONCLUSION:
A hypomorphic VEGFR3 mutation, with moderate effect on receptor function, in a homozygous state can result in insufficient lymphatic functioning. Thus, in addition to Nonne-Milroy disease with dominant inheritance, VEGFR3 alterations can cause isolated recessive primary congenital lymphoedema. These data expand our understanding of the aetiology of congenital lymphoedema and suggest that large scale screening of VEGFR3 in all primary lymphoedema patients is necessary.
Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Receptor 3 de Factores de Crecimiento Endotelial Vascular
/
Genes Recesivos
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Linfedema
Tipo de estudio:
Prognostic_studies
Límite:
Humans
Idioma:
En
Revista:
J Med Genet
Año:
2009
Tipo del documento:
Article
País de afiliación:
Bélgica
Pais de publicación:
ENGLAND
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ESCOCIA
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GB
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GREAT BRITAIN
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INGLATERRA
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REINO UNIDO
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SCOTLAND
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UK
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UNITED KINGDOM