Mutation analysis in hereditary haemorrhagic telangiectasia in Germany reveals 11 novel ENG and 12 novel ACVRL1/ALK1 mutations.
Hereditary haemorrhagic telangiectasia (HHT) is an autosomal-dominant disease characterized by recurrent epistaxis, mucocutaneous telangiectasias and visceral arteriovenous malformations. Mutations in endoglin (ENG) and activin A receptor type II-like kinase 1 (ACVRL1 or ALK1) have been found in patients with HHT. We have screened a total of 51 unselected German index cases with the suspected diagnosis of HHT. We identified 30 different mutations in 32 cases (62.7%) by direct sequencing. Among these mutations, 11 of 13 ENG mutations and 12 of 17 ACVRL1 mutations were not previously reported in the literature. Two of the ACVRL1 mutations were each shared by two families. An analysis of the genotype-phenotype correlation is consistent with a more common frequency of pulmonary arteriovenous malformations in patients with ENG mutations than in patients with ACVRL1 mutations in our collective.
Institute of Human Genetics, Georg-August University, Göttingen, Germary.
L-E
LE
Wehner
B J
BJ
Folz
L
L
Argyriou
S
S
Twelkemeyer
U
U
Teske
U W
UW
Geisthoff
J A
JA
Werner
W
W
Engel
K
K
Nayernia
D030301:Activin Receptors, Type II / Q000235:genetics*; D000595:Amino Acid Sequence; D015703:Antigens, CD / Q000235:genetics*; D001165:Arteriovenous Malformations / Q000150:complications / Q000235:genetics; D000071063:Endoglin; D005838:Genotype; D005858:Germany; D006801:Humans; D008969:Molecular Sequence Data; D009154:Mutation; D010641:Phenotype; D011651:Pulmonary Artery / Q000002:abnormalities; D011667:Pulmonary Veins / Q000002:abnormalities; D011956:Receptors, Cell Surface / Q000235:genetics*; D017386:Sequence Homology, Amino Acid; D013683:Telangiectasia, Hereditary Hemorrhagic / Q000150:complications / Q000235:genetics*
D015703:Antigens, CD; C064206:ENG protein, human; D000071063:Endoglin; D011956:Receptors, Cell Surface; C425364:ACVRL1 protein, human; D030301:Activin Receptors, Type II