Qian Yu1, Zhao Cheng1, Yi-Fang Yi1, Hong-Ling Peng2. 1. Department of Hematology, The Second Xiangya Hospital of Central South University, Changsha 410011, Hunan Province, China. 2. Department of Hematology, The Second Xiangya Hospital of Central South University, Changsha 410011, Hunan Province, China. E-mail: penghongling@aliyun.com.
Abstract
OBJECTIVE: To analyze a hereditary hemorrhagic telangiectasia(HHT) family Activin receptor-like kinase 1(ACVRL1), Endoglin (ENG) and Mothers against decapentaplegic homolog 4 (MADH4, SMAD4) gene mutation, meanwhile, to observe the curative effect of thalidomide in treatment of HHT patients. METHODS: The clinical feature of the HHT family was analyzed, the polymerase chain reaction (PCR) combined with Sanger sequencing of ACVRL1, ENG and SMAD4 were used to investigate the proband. The suspicious mutations were further detected in the other 7 family members. Proband was treated with thalidomide (100 mg/day) for 6 months, and the frequency and quantity of bleeding and blood transfusion frequency were assayed to evaluate the curative efficacy. RESULTS: One ACVRL1 mutation (c.1231C>T) was identified in proband(II-1) and the other 4 family members(II-2, III-1, III-2, III-3), which was reported as a pathogenic gene and revealed cosegregation with HHT clinical phenotype. One ENG mutation (c.1096G>C) was previously reported as gene polymorphism, which was identified in some family members(II-1, II-3, III-1, III-2) without cosegregation with clinical phenotype. No gene mutation was found in SMAD4. After thalidomide treatment, the frequency and quantity of bleeding and blood transfusion frequncy in the proband were reduced, hemoglobin concentration and serum iron level were increased. CONCLUSION: There is phenotypic heterogeneity in hereditary hemorrhagic telangiectasia and the features are age-dependent, the pathogenic gene of this pedigree is ACVRL1 mutation (c.1231C>T;p. R 411 W). Thalidomide is effective for the treatment of hemorrhage in hereditary hemorrhagic telangiectasia.
OBJECTIVE: To analyze a hereditary hemorrhagic telangiectasia(HHT) family Activin receptor-like kinase 1(ACVRL1), Endoglin (ENG) and Mothers against decapentaplegic homolog 4 (MADH4, SMAD4) gene mutation, meanwhile, to observe the curative effect of thalidomide in treatment of HHTpatients. METHODS: The clinical feature of the HHT family was analyzed, the polymerase chain reaction (PCR) combined with Sanger sequencing of ACVRL1, ENG and SMAD4 were used to investigate the proband. The suspicious mutations were further detected in the other 7 family members. Proband was treated with thalidomide (100 mg/day) for 6 months, and the frequency and quantity of bleeding and blood transfusion frequency were assayed to evaluate the curative efficacy. RESULTS: One ACVRL1 mutation (c.1231C>T) was identified in proband(II-1) and the other 4 family members(II-2, III-1, III-2, III-3), which was reported as a pathogenic gene and revealed cosegregation with HHT clinical phenotype. One ENG mutation (c.1096G>C) was previously reported as gene polymorphism, which was identified in some family members(II-1, II-3, III-1, III-2) without cosegregation with clinical phenotype. No gene mutation was found in SMAD4. After thalidomide treatment, the frequency and quantity of bleeding and blood transfusion frequncy in the proband were reduced, hemoglobin concentration and serum iron level were increased. CONCLUSION: There is phenotypic heterogeneity in hereditary hemorrhagic telangiectasia and the features are age-dependent, the pathogenic gene of this pedigree is ACVRL1 mutation (c.1231C>T;p. R 411 W). Thalidomide is effective for the treatment of hemorrhage in hereditary hemorrhagic telangiectasia.