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Identification of a novel mutation in the gene for bone morphogenetic protein receptor II in an Israeli patient with familial primary pulmonary hypertension.
- Source :
-
The Israel Medical Association journal : IMAJ [Isr Med Assoc J] 2004 Mar; Vol. 6 (3), pp. 156-9. - Publication Year :
- 2004
-
Abstract
- Background: Primary pulmonary hypertension is a rare disorder, characterized by progressive pulmonary hypertension and right heart failure. It may be familial or sporadic. Mutations in bone morphogenetic protein receptor II (BMPR2), a member of the transforming growth factor-beta receptor superfamily of receptors, underlie many cases of the disorder.<br />Objectives: To perform molecular analysis of a patient with familial PPH and provide her and her family with suitable genetic counseling.<br />Methods: DNA was extracted from 10 ml whole blood, and the BMPR2 gene was screened for mutations. Individual exons were amplified by polymerase chain reaction and sequenced. Mutation confirmation and molecular characterization of additional family members was performed using restriction enzyme analysis followed by appropriate genetic counseling.<br />Results: We identified a novel T to C missense mutation expected to result in substitution of arginine for a conserved cysteine in the ligand-binding domain of BMPR2. Screening of family members demonstrated the presence of the mutation in the father and a younger asymptomatic sister of the index patient.<br />Conclusions: Molecular diagnosis in PPH allows for identification of at-risk family members and raises the option of earlier diagnosis and possibly instituting earlier treatment in affected individuals. However, molecular screening of asymptomatic family members raises difficult ethical questions that can only be resolved by conducting large multicenter prospective studies in BMPR2 carriers.
- Subjects :
- Adult
Base Sequence
Bone Morphogenetic Protein Receptors, Type II
DNA Mutational Analysis
Female
Genetic Counseling
Heterozygote
Humans
Hypertension, Pulmonary diagnosis
Israel
Molecular Sequence Data
Mutation, Missense
Pedigree
Polymerase Chain Reaction methods
Prognosis
Genetic Predisposition to Disease
Hypertension, Pulmonary genetics
Protein Serine-Threonine Kinases genetics
Subjects
Details
- Language :
- English
- ISSN :
- 1565-1088
- Volume :
- 6
- Issue :
- 3
- Database :
- MEDLINE
- Journal :
- The Israel Medical Association journal : IMAJ
- Publication Type :
- Academic Journal
- Accession number :
- 15055271