Mutation Analysis Of ALK1 Gene In A Chinese Family With Hereditary Hemorrhagic Telangiectasis Type Ⅱ

Background Hereditary hemorrhagic telangiectasis(HHT),or Osler-Rendu-Weber syndrome,is a rare autosomal dominantly inherited disease.Its penetrance increased throughout adult life,cart raised to 97%-100%in age 40.The HHT is characterized by multiple telangiectasis and hemorrhage in skin and mucous membrane,usually has no feeling.HHT has recurring bleeding in skin and mucous membrane,the most common symptom is epistaxis,pulmonary arteriovenous malformations(PAVM) and celebral arteriovenous malformations(CAVM) also can be seen.It has two clinic phenotype: HHT1 and HHT2,HHT1 onset earlier,more serious,and has more chance of suffer from PAVM.Histology revealed vessel wall is thin,lack of elastic fibers and smooth muscle,vessel extened.The thin vessel can easily disrupted by bloodstream.HHT1 is caused by ENG gene which locus to chromosome 9q34.HHT2 is caused by ALK1 gene,linkage analysis mapped it to chromosome 12q13.Above 160 mutation in ENG gene and 130 mutation ALK1 gene have been reported,incuding missense mutation, nonsense mutation,splice mutation,small deletion mutation,small insertion mutation, and so on.Objectives.To identify the mutation of ALK1 gene in a Chinese family with hereditary hemorrhagic telangiectasis(HHT) typeⅡ.Methods We collected a Chinese HHT family and their blood samples.Genomic DNA was extracted from peripheral blood.All the coding exons of ALK1 gene of the patients and 100 unrelated population-matched controls were amplified by polymerase chain reaction and products analyzed by direct sequencing. Results A missense mutation c.1010T＞C(p.L337P) of ALK1 gene was identified in all the patients of the family,but did not found in the 100 unrelated controls.Conclusions The c.1010T＞C(p.L337P) mutation of ALK1 gene seems to be involved in the pathologic cause of this Chinese family with HHT typeⅡ.