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A correction has been published: N Engl J Med 2002;346(16):1258.

Previous Volume 345:319-324 August 2, 2001 Number 5 Next

	Full Text PDF Editorial by Loscalzo, J. Add to Personal Archive Add to Citation Manager Notify a Friend E-mail When Cited Related Article Related Article PubMed Citation

ABSTRACT

Background Most patients with primary pulmonary hypertension are thought to have sporadic, not inherited, disease. Because clinical disease develops in only 10 to 20 percent of persons carrying the gene for familial primary pulmonary hypertension, we hypothesized that many patients with apparently sporadic primary pulmonary hypertension may actually have familial primary pulmonary hypertension.

Methods In a study conducted over 20 years, we developed a registry of 67 families affected by familial primary pulmonary hypertension. Through patient referrals, extensive family histories, and correlation of family pedigrees, we discovered shared ancestry among five subfamilies. We assessed some family members for mutations in the gene encoding bone morphogenetic protein receptor II (BMPR2), which has recently been found to cause familial primary pulmonary hypertension.

Results We linked five separately identified subfamilies that included 394 known members spanning seven generations, which were traced back to a founding couple in the mid-1800s. Familial primary pulmonary hypertension has been diagnosed in 18 family members, 12 of whom were first thought to have sporadic disease. The conditions of 7 of the 18 were initially misdiagnosed as other cardiopulmonary diseases. Six members affected with familial primary pulmonary hypertension and 6 of 10 at risk for carriage have undergone genotype analysis, and they have the same mutation in BMPR2, a transversion of thymine to guanine at position 354 in exon 3.

Conclusions Many cases of apparently sporadic primary pulmonary hypertension may be familial. The recent discovery of mutations in BMPR2 should make it possible to identify those with susceptibility to the disease.

Source Information

From the Center for Lung Research, Division of Allergy, Pulmonary, and Critical Care Medicine, Department of Medicine (J.H.N., L.W., K.B.L., E.L., R.G., J.E.L.), and the Division of Medical Genetics, Department of Pediatrics (J.A.P.), Vanderbilt University School of Medicine, Nashville.

Address reprint requests to Dr. Newman at the Allergy, Pulmonary, and Critical Care Division, T-1218, Vanderbilt University Medical Center North, Nashville, TN 37232-2650, or at john.newman{at}med.va.gov.

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