Objective: To investigate the clinical and genetic characteristics of familial primary pulmonary hypertension (PPH) in Han nationality.
Methods: The clinical and laboratory features of patients of familial PPH in a family of Han nationality in Zhumadian, Henan Province, including the propositus, female, aged 37, her 29-years-old brother, and her 14-years-old daughter, were summarized. Samples of peripheral blood were collected from all family members and 100 healthy volunteers. Genomic DNA of the peripheral white blood cells was extracted from the samples. Primers for the exon 1 - 13 including the lateral intron of bone morphogenetic protein receptor-II (BMPR2) gene were designed. Then the genomic DNA was amplified by PCR. The PCR products were purified, sequenced, and compared with the sequence of normal BMPR2 gene.
Results: The 3 patients in this family, coming down with the illness at the ages of 35, 23, and 13 respectively, suffered from severe pulmonary hypertension and cor pulmonale with the clinical manifestations of cough, hemoptysis, heart enlargement, and cardiac function of class III. The propositus' mother came down with PPH in the age of 42 and died 1 year later. Sequence analysis showed codon 491 C-->T conversion in exon 11 in all three patients (heterozygote), which induces arginine to change to tryptophan (R491W). None BMPR2 mutation was identified in the 100 normal controls and other family members without PPH.
Conclusion: As in the white people, the missense mutation of R491W in BMPR2 gene is also one crucial pathogenetic gene of familial PPH in Han nationality. There is no normal carrier of such genotype.