Science & Technology, Life Sciences & Biomedicine, Pediatrics, PROTEIN-RECEPTOR-II, GERMLINE MUTATIONS, LINKAGE ANALYSIS, SURVIVAL, FAMILY, BMPR2, Adolescent, Adult, Blood Pressure, Bone Morphogenetic Protein Receptors, Type II, Child, Child, Preschool, Echocardiography, Family, Female, Genetic Linkage, Haplotypes, Humans, Hypertension, Pulmonary, Infant, Male, Pedigree, Phenotype, Protein-Serine-Threonine Kinases, 1114 Paediatrics and Reproductive Medicine
Mutations of the bone morphogenetic protein receptor II (BMPR2) gene on chromosome 2q33 can cause familial primary pulmonary hypertension (PPH) and may occur in 26% adult patients with sporadic disease. Other disease-related genes have been localized to chromosomes 2q31 (PPH2) and 12q13 (ALK1). The genetic background in affected children remains unclear. Thirteen children (age at diagnosis, 6 mo to 13 y; mean, 5.6 +/- 3.9 y) with invasively confirmed PPH were screened for BMPR2 mutations using denaturing HPLC and sequence analysis. In addition, all children were scanned for BMPR2 deletions by Southern blot analysis. Pulmonary artery pressure was assessed using echocardiography at rest and during exercise in 57 family members of six infants. The six families were subjected to linkage analysis. None of the 13 children had a BMPR2 mutation or deletion. Linkage to chromosome 2 or 12 could not be confirmed in any of the families investigated. In all assessed families, both parents of the index patient and/or members of both branches revealed an abnormal pulmonary artery systolic pressure (PASP)-response to exercise. PPH in children may have a different genetic background than in adults. We postulate a recessive mode of inheritance in a proportion of infantile cases.