Clinical phenotypes, ALK1 gene mutation and level of related plasma proteins in Chinese hereditary hemorrhagic telangiectasia / 中华医学杂志(英文版)
Chinese Medical Journal
;
(24): 808-812, 2004.
Article
in English
| WPRIM
| ID: wpr-284902
ABSTRACT
<p><b>BACKGROUND</b>We determined the diagnosis of hereditary hemorrhagic telangiectasis (HHT) in a suspected HHT family, identified ALK1 gene mutation and established a gene diagnosis method of HHT. The level of related plasma proteins (transforming growth factor beta and thrombomodulin) were also analyzed.</p><p><b>METHODS</b>Bleeding history and family history were collected; Dilatant nasal mucosal capillaries in proband were observed under nasal cavity endoscope; exons 3, 7, 8 of ALK1 gene in proband and her family members were amplified with polymerase chain reaction (PCR), and the PCR products were analyzed. Using enzyme-linked immunosorbent assay (ELISA), plasma TGF-beta1 and TGF-beta2 concentrations were measured. Plasma thrombomodulin (TM) level was detected by Western blotting.</p><p><b>RESULTS</b>Of all family members, four had epstaxis, two had evident telangiectases on skin or mucosa. Gene screening results showed that C to T substitution at position 1231 in exon 8 of ALK1 gene (CGG-->TGG) existed in proband, her affected brother and their father. The mutation did not exist in proband's sister-in-law and nephew. Plasma TGF-beta1 concentrations in the affected HHT was 20,538, 17,194, 13,131 pg/ml, while that of normal control and unaffected family members was 15,950, 20,297, 12,836 pg/ml, respectively. Plasma TGF-beta2 in HHT patients was 14,502, 9550, 10,592 and that of normal controls 8579, 20,297, 7680 pg/ml respectively. Level of plasma TM was in HHT subjects significantly lower than in normal subjects.</p><p><b>CONCLUSIONS</b>Chinese HHT individuals have mutant ALK1 gene, a C1231T variation on exon 8 of ALK1 is responsible for HHT clinical phenotypes in this family. ALK1 gene analysis, together with special clinical phenotypes and family history, provides a reliable method in diagnosing HHT. In affected HHT subjects, plasma TGFbeta levels were not obviously different from those of normal subject; while plasma TM concentration was significantly lower than that in normal subjects. The significance and mechanism remain to be elucidated.</p>
Full text:
Available
Index:
WPRIM (Western Pacific)
Main subject:
Telangiectasia, Hereditary Hemorrhagic
/
Blood
/
China
/
Transforming Growth Factor beta
/
Thrombomodulin
/
Activin Receptors, Type I
/
Activin Receptors, Type II
/
Asian People
/
Genetics
/
Mutation
Type of study:
Prognostic study
Limits:
Aged
/
Female
/
Humans
/
Male
Country/Region as subject:
Asia
Language:
English
Journal:
Chinese Medical Journal
Year:
2004
Type:
Article
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