Human Disease Model Report: mitochondrial DNA depletion syndrome 12B (cardiomyopathic type), autosomal recessive
Human Disease Model Report: mitochondrial DNA depletion syndrome 12B (cardiomyopathic type), autosomal recessive
This report describes mitochondrial DNA depletion syndrome 12 (cardiomyopathic type), autosomal recessive; the human gene implicated in this disease is SLC25A4, which encodes a mitochondrial ADP/ATP translocator. SLC25A4 is implicated in more than one mitochondrial disease (OMIM:103220). For information on experimental results using Drosophila models of this and related diseases see the human disease model report 'mitochondrial disease and seizure sensitivity, SLC25A4(ANT1)-related' (FBhh0000372).
[updated Jul. 2017 by FlyBase; FBrf0222196]
Mitochondrial DNA (mtDNA) depletion syndrome (MDS) is a clinically heterogeneous group of mitochondrial disorders characterized by a reduction of the mtDNA copy number in affected tissues without mutations or rearrangements in the mtDNA. MDS is phenotypically heterogeneous, and can affect a specific organ or a combination of organs, with the main presentations described being either hepatocerebral (i.e. hepatic dysfunction, psychomotor delay), myopathic (i.e. hypotonia, muscle weakness, bulbar weakness), encephalomyopathic (i.e. hypotonia, muscle weakness, psychomotor delay) or neurogastrointestinal (i.e gastrointestinal dysmotility, peripheral neuropathy). [http://www.orpha.net/consor/cgi-bin/OC_Exp.php?Lng=GB&Expert=35698.0 2016.11.23]
[MITOCHONDRIAL DNA DEPLETION SYNDROME 12B (CARDIOMYOPATHIC TYPE), AUTOSOMAL RECESSIVE; MTDPS12B](https://omim.org/entry/615418)
[SOLUTE CARRIER FAMILY 25 (MITOCHONDRIAL CARRIER, ADENINE NUCLEOTIDE TRANSLOCATOR), MEMBER 4; SLC25A4](https://omim.org/entry/103220)
Mitochondrial DNA depletion syndrome-12 (MTDPS12) is an autosomal recessive mitochondrial disorder characterized by childhood onset of slowly progressive hypertrophic cardiomyopathy and generalized skeletal myopathy resulting in exercise intolerance and, in some patients, muscle weakness and atrophy (summary by Echaniz-Laguna et al., 2012; pubmed:22187496). [from OMIM:615418; 2016.08.25]
MTDPS12 is caused by homozygous mutation in the nuclear-encoded gene SLC25A4 (ANT1).
Skeletal muscle biopsy shows ragged red fibers, mtDNA depletion, and accumulation of abnormal mitochondria (summary by Echaniz-Laguna et al., 2012; pubmed:22187496). [from OMIM:615418; 2016.08.25]
The SLC25A4 gene encodes a mitochondrial ADP/ATP translocator (also known as adenine nucleotide translocator 1, ANT1), which is a homodimer of 30-kD subunits embedded in the mitochondrial inner membrane. The dimer forms a gated pore through which ADP is moved across the inner membrane into the mitochondrial matrix and ATP is moved from the matrix into the cytoplasm (summary by Neckelmann et al., 1987; pubmed:2823266). [from OMIM:103220; 2016.08.25]