Bone morphogenetic protein receptor-II mutation Arg491Trp causes malignant phenotype of familial primary pulmonary hypertension.
A four-generation pedigree of familial primary pulmonary hypertension (FPPH) with 14 alive members was collected. In the family, three of the 14 alive familial members were diagnosed as FPPH. Mutations in bone morphogenetic protein receptor-II (BMPR-II) gene were screened by using sequencing analysis. A C-to-T transition at position 1471 in exon 11 of the BMPR-II gene was identified, resulting in an Arg491Trp mutation. We confirmed segregation of the mutation within the family and excluded the presence of the mutations in a panel of 240 chromosomes from normal individuals. No mutations were found in BMPR-II gene in other 10 patients with sporadic primary pulmonary hypertension. The Arg491Trp mutation is located in the kinase domain and predicted to disturb the kinase activity of BMPR-II. Total 7 familial members died at age 8-45 years with various symptoms, indicating other genetic or environmental modifiers involved in the modification of the clinical phenotype.
Department of Cardiololgy, Fu Wai Heart Hospital, Peking Union Medical College and Chinese Academy of Medical Sciences, No.167 Beilishilu, Beijing 100037, China.
Jing
J
Zhicheng
Lu
L
Lihe
Han
H
Zhiyan
Cheng
C
Xiansheng
Zou
Z
Yubao
Yang
Y
Yuejin
Hui
H
Rutai
D000293:Adolescent; D000328:Adult; D019943:Amino Acid Substitution; D001483:Base Sequence; D052006:Bone Morphogenetic Protein Receptors, Type II; D017931:DNA Primers / Q000235:genetics; D004452:Echocardiography; D004562:Electrocardiography; D005091:Exons / Q000235:genetics; D005260:Female; D006801:Humans; D006976:Hypertension, Pulmonary / Q000235:genetics* / Q000473:pathology; D008297:Male; D008969:Molecular Sequence Data; D020125:Mutation, Missense; D010375:Pedigree; D010641:Phenotype; D017346:Protein Serine-Threonine Kinases / Q000235:genetics* / Q000502:physiology; D013902:Radiography, Thoracic; D017422:Sequence Analysis, DNA
D017931:DNA Primers; D017346:Protein Serine-Threonine Kinases; C498218:BMPR2 protein, human; D052006:Bone Morphogenetic Protein Receptors, Type II