Authors' recommendations: Mitochondria are powerhouses of the cell and key to their function is the electron transport chain which makes adenosine triphosphate (ATP) by the process of oxidative phosphorylation. With a prevalence of 1:5000 to 1:16,000 live births, disorders that affect the functioning of the mitochondria are becoming increasingly recognized as a cause of morbidity and mortality. Some mitochondrial disorders may affect a single body system or organ such as Leber's hereditary optic neuropathy (LHON), which affects mainly the eyes; others may affect several body systems simultaneously, such as Wolfram syndrome (WS), which causes diabetes, optic atrophy and deafness. Mitochondrial disorders may be caused by sequence variants in nuclear DNA (nDNA), or mitochondrial DNA (mtDNA). This report focuses on disorders associated with sequence variants in mtDNA. The onset of symptoms for nDNA disorders generally occurs in childhood, and mtDNA disorders have a later onset in late childhood or adulthood. Sequence variants in mtDNA can cause a variety of disorders that typically affect tissues that have high energy requirements such as the central and peripheral nervous systems, eyes, ears, endocrine organs, heart, intestines, liver, kidneys, bone marrow, and dermis. Cells in the human body typically contain 50 to 100 mitochondria, and each of these has from 2 to 10 copies of mtDNA. Mitochondrial DNA contains 16,568 bases and codes for 37 genes. There is a great deal of variability in the severity and symptoms caused by mitochondrial disorders, which is explained by a number of factors. These include: the location of sequence variants in the 37 genes in mtDNA; the type of sequence variant (single nucleotide, multiple small deletions, or large rearrangements); heteroplasmy, or the proportion of mitochondria in a cell that contain the sequence variant; variable maternal inheritance caused by heteroplasmy and the selection of which mitochondria populate an embryo; and mitotic segregation, which is the variable distribution of mitochondria with sequence variants during normal cell division. While there a number of mtDNA syndromes that are clinically well defined, many patients do not have distinctive symptoms and are not easily categorized. One problem with analyzing the mtDNA genome is that the pathogenicity of many sequence variants is not known. Many sequence variants in the mtDNA genome are benign polymorphisms that can be used to categorize the evolutionary origin of individuals or groups (phylogenetics).

Project Status: Completed

Year Published: 2010

URL for published report: http://www.hayesinc.com/hayes/crd/?crd=9986

English language abstract: An English language summary is available

Publication Type: Not Assigned

Country: United States

Organisation Name: HAYES, Inc.

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Contact Email: saleinfo@hayesinc.com

Copyright: 2010 Winifred S. Hayes, Inc