Animal studies suggest that decreased vascular mitochondrial DNA copy number can promote hypertension. We conducted a chart review of blood pressure and hemodynamics in patients with either mitochondrial encephalopathy, lactic acidosis, and stroke-like episodes (MELAS, n = 36) or individuals with variants in the mitochondrial DNA polymerase gamma (POLG, n = 26). The latter included both pathogenic variants and variants of unknown significance (VUS). Hypertension rates (MELAS 50%, POLG 50%) were elevated relative to Canadian norms in 20-39 (MELAS) and 40-59 (MELAS and POLG) years of age groups. Peripheral resistance was high in the hypertensive versus normotensive patients, potentially indicative of microvascular disease. Despite antihypertensive treatment, systolic blood pressure remained elevated in the POLG versus MELAS group. The risk of hypertension was not associated with MELAS heteroplasmy. Hypertension rates were not different between individuals with known pathogenic POLG variants and those with VUS, including common variants. Hypertension (HT) also did not differ between patients with POLG variants with (n = 17) and without chronic progressive external opthalmoplegia (n = 9) (CPEO). HT was associated with variants in all three functional domains of POLG. These findings suggest that both pathogenic variants and several VUS in the POLG gene may promote human hypertension and extend our past reports that increased risk of HT is associated with MELAS.
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http://dx.doi.org/10.1016/j.mito.2020.05.011 | DOI Listing |
Background: Variants in the mitochondrial genome (mtDNA) cause a diverse collection of mitochondrial diseases and have extensive phenotypic overlap with Mendelian diseases encoded on the nuclear genome. The mtDNA is often not specifically evaluated in patients with suspected Mendelian disease, resulting in overlooked diagnostic variants.
Methods: Using dedicated pipelines to address the technical challenges posed by the mtDNA - circular genome, variant heteroplasmy, and nuclear misalignment - single nucleotide variants, small indels, and large mtDNA deletions were called from exome and genome sequencing data, in addition to RNA-sequencing when available.
Cancers (Basel)
November 2024
Department of Oncology-Pathology, Karolinska Institutet, 17164 Stockholm, Sweden.
Background: The etiology of most mesenchymal tumors is unknown, and knowledge about syndromes with an increased risk of tumors in bone or soft tissue is sparse.
Methods: We present a prospective germline analysis of 312 patients with tumors suspected of being sarcomas at a tertiary sarcoma center. Germline and tumor whole genome sequencing, tumor transcriptome, and methylome analyses were performed.
Orphanet J Rare Dis
November 2024
Department of Clinical and Experimental Medicine, Neurological Institute, University of Pisa, Pisa, Italy.
Physiol Res
November 2024
Department of Pharmacy, Yiyang Medical College, Yiyang, China; College of Dental Medicine, Western University of Health Sciences, Pomona, CA, USA.
Mutations in DNA polymerase gamma (POLG) are known as the predominant cause of inherited mitochondrial disorders. But how these POLG mutations disturb mitochondrial function remains to be determined. Furthermore, no effective therapy, to date, has been reported for POLG diseases.
View Article and Find Full Text PDFZhonghua Fu Chan Ke Za Zhi
October 2024
Department of Obstetrics and Gynecology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences, National Clinical Research Center for Obstetric and Gynecologic Diseases, Beijing 100730, China.
To determine the carrier frequency and hot-spot variants of a custom-designed expanded carrier screening (ECS) panel with 216 diseases (216-ECS panel) within a Chinese population of childbearing age. Whole-exome sequencing data from a cohort of 3 097 unrelated healthy individuals (including 1 424 couples) from Peking Union Medical College Hospital between January 2013 and December 2023 were analyzed. Totally 220 genes which inherited in a recessive manner of 216-ECS panel were included in the analysis.
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