Title: A Klinefelter patient with an additional mitochondrial mutation: Implications for genotype-driven treatment and mitochondrial mutational load in different tissues and family members
Abstract: Many genetic disorders are clinically heterogeneous [ [1] Altmann J. Buchner B. Nadaj-Pakleza A. et al. Expanded phenotypic spectrum of the m.8344A>G "MERRF" mutation: data from the German mitoNET registry. J. Neurol. 2016; 263: 961-972 Crossref PubMed Scopus (61) Google Scholar ] and thus may be challenging to be diagnosed solely based on the clinical examination. In addition, if two or more genetic disorders are present in the same patient, the phenotypic presentation will be an additive result of both underlying disorders [ [2] Posey J.E. Harel T. Liu P. et al. Resolution of disease phenotypes resulting from multilocus genomic variation. N. Engl. J. Med. 2017; 376: 21-31 Crossref PubMed Scopus (436) Google Scholar ]. The scenario gets even more complicated when mitochondrial DNA (mtDNA) mutations play a role, since mtDNA represents high-copy-number, extra-nuclear genetic material exclusively transmitted through the mother. The transmission of mitochondria to offspring cells occurs at random but there is negative selection of mutations depending on energy demand and confluency of cells. Levels of heteroplasmy influence penetrance of a mutation and vary across different tissues within individual mutation carriers [ [3] Chinnery P.F. Howell N. Lightowlers R.N. Turnbull D.M. Molecular pathology of MELAS and MERRF. The relationship between mutation load and clinical phenotypes. Brain. 1997; 120: 1713-1721 Crossref PubMed Scopus (322) Google Scholar ]. Therefore, tissue selection for genetic analysis may be important.
Publication Year: 2018
Publication Date: 2018-09-01
Language: en
Type: letter
Indexed In: ['crossref', 'pubmed']
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Cited By Count: 1
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