The study established a national registry of familial PPH (FPPH). The primary goal of the family registry was to establish and expand the database of FPPH pedigrees to definitively establish the mode of inheritance of FPPH, which initial segregation analysis suggested was autosomal dominant. The FPPH family registry provided the framework for the linkage analysis of the molecular search for basic mechanisms of PPH. The investigators developed a tissue bank for specimens (DNA and transformed lymphocytes) from families and patients with pulmonary hypertension, both for their investigations and as a national resource for other interested investigators. Their search used three different approaches to investigate for a FPPH gene locus. First, they performed karyotyping and high resolution chromosome studies to search for a chromosomal translocation, interstitial deletion, or inversion, the finding of which would implicate a specific gene locus. Second, they pursued the proposed association of human leukocyte antigen (HLA) tissue type with familial PPH in a parallel attempt to identify a related locus about which to perform an intensified molecular search, using regional mapping studies of closely linked markers. Finally, they performed linkage analysis in selected PPH families which had the most informative inheritance patterns, using polymerase chain reaction (PCR) based microsatellite markers for selected candidate genes, including those for transforming growth factor beta, endothelin, beta globin, and HLA. An additional promising approach included a search for linkage of FPPH to genes with GC-rich trinucleotide repeats, as had been successful for other diseases with genetic anticipation, including Fragile X syndrome, myotonic dystrophy, and Huntington's disease.