Endoglin, a TGF-beta binding protein of endothelial cells, is the gene for hereditary haemorrhagic telangiectasia type 1.
Hereditary haemorrhagic telangiectasia (HHT) is an autosomal dominant disorder characterized by multisystemic vascular dysplasia and recurrent haemorrhage. Linkage for some families has been established to chromosome 9q33-q34. In the present study, endoglin, a transforming growth factor beta (TGF-beta) binding protein, was analysed as a candidate gene for the disorder based on chromosomal location, expression pattern and function. We have identified mutations in three affected individuals: a C to G substitution converting a tyrosine to a termination codon, a 39 base pair deletion and a 2 basepair deletion which creates a premature termination codon. We have identified endoglin as the HHT gene mapping to 9q3 and have established HHT as the first human disease defined by a mutation in a member of the TGF-beta receptor complex.
McAllister
K A
KA
Department of Genetics, Duke University Medical Center, Durham, North Carolina 27710.
Grogg
K M
KM
Johnson
D W
DW
Gallione
C J
CJ
Baldwin
M A
MA
Jackson
C E
CE
Helmbold
E A
EA
Markel
D S
DS
McKinnon
W C
WC
Murrell
J
J
D000595:Amino Acid Sequence; D015703:Antigens, CD; D001483:Base Sequence; D002874:Chromosome Mapping; D002899:Chromosomes, Human, Pair 9; D003062:Codon; D018076:DNA, Complementary; D000071063:Endoglin; D005260:Female; D006801:Humans; D008297:Male; D008562:Membrane Glycoproteins / Q000235:genetics* / Q000378:metabolism; D008969:Molecular Sequence Data; D010375:Pedigree; D011956:Receptors, Cell Surface; D013683:Telangiectasia, Hereditary Hemorrhagic / Q000235:genetics*; D013728:Terminator Regions, Genetic; D016212:Transforming Growth Factor beta / Q000378:metabolism*; D019010:Vascular Cell Adhesion Molecule-1
D015703:Antigens, CD; D003062:Codon; D018076:DNA, Complementary; C064206:ENG protein, human; D000071063:Endoglin; D008562:Membrane Glycoproteins; D011956:Receptors, Cell Surface; D016212:Transforming Growth Factor beta; D019010:Vascular Cell Adhesion Molecule-1