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Telomere DNA, at the ends of each chromosome, is conserved in nature and required for chromosome replication and stability. Reduction in telomere length has been observed in several malignancies as well as in leukocytes from healthy persons with advancing age. There is a paucity of data regarding telomere length and the effects of in vivo aging in different(More)
We investigated whether an association exists between genetic variants of the human obesity (OB or leptin) gene and body mass index (BMI) or weight in subjects with Prader Willi syndrome (PWS) and in age- and gender-matched lean and obese subjects without PWS. The study included 51 subjects with PWS (mean age = 17.7 +/- 9.5 years, BMI = 29.7 +/- 8.3 kg/m2);(More)
RATIONALE Previous studies have shown that approximately 55% of patients with familial pulmonary arterial hypertension (FPAH) have BMPR2 coding sequence mutations. However, direct sequencing does not detect other types of heterozygous mutations, such as exonic deletions/duplications. OBJECTIVE To estimate the frequency of BMPR2 exonic(More)
BACKGROUND Bone morphogenic protein receptor 2 (BMPR2) gene mutations are the most common cause of heritable pulmonary arterial hypertension. However, only 20% of mutation carriers get clinical disease. Here, we explored the hypothesis that this reduced penetrance is due in part to an alteration in BMPR2 alternative splicing. METHODS AND RESULTS Our data(More)
High-altitude pulmonary hypertension (HAPH) is a consequence of chronic alveolar hypoxia, leading to hypoxic vasoconstriction and remodeling of the pulmonary circulation. Brisket disease in cattle is a naturally occurring animal model of hypoxic pulmonary hypertension. Genetically susceptible cattle develop severe pulmonary hypertension and right heart(More)
Mutations in bone morphogenetic protein receptor type 2 (BMPR2) cause familial pulmonary arterial hypertension (FPAH), but the penetrance is reduced and females are significantly overrepresented. In addition, gene expression data implicating the oestrogen-metabolising enzyme CYP1B1 suggests a detrimental role of oestrogens or oestrogen metabolites. We(More)
Familial pulmonary arterial hypertension (FPAH) is a progressive, fatal disease caused by mutations in the bone morphogenetic protein receptor type 2 gene (BMPR2). FPAH is inherited as an autosomal dominant trait, and shows incomplete penetrance in that many with BMPR2 mutations do not develop FPAH, suggesting a role for, as yet unidentified, modifier genes(More)
Eukaryotic chromosomes contain specialized structures at the termini called telomeres. This region of DNA is required for replication and stability of the chromosome. Telomere reduction can contribute to genetic instability and has been described in certain malignancies (e.g., colon, leukemia, giant cell tumor of bone). To determine whether telomere(More)
PURPOSE Approximately 50% of patients with familial primary pulmonary hypertension (FPPH) have been reported to have mutations within the bone morphogenic protein receptor type 2 (BMPR2) gene. The vast majority of these mutations were identified by PCR amplification and sequencing of individual exons. The aim of our study was to determine if additional(More)
Defective mismatch repair has been detected in human colorectal and endometrial carcinomas which exhibit microsatellite instability (MIN). The purpose of this study was to search for MIN in melanoma. Paraffin-embedded neoplastic and non-neoplastic control cells were obtained from 20 untreated individuals with cutaneous malignant melanoma. Breslow thickness(More)