Brain Imaging in Mitochondrial Respiratory Chain Deficiency
Brain Imaging in Mitochondrial Respiratory Chain Deficiency
Mitochondrial diseases are characterised by a broad clinical and genetic heterogeneity that makes diagnosis difficult. Owing to the wide pattern of symptoms in mitochondrial disorders and the constantly growing number of disease genes, their genetic diagnosis is difficult and genotype/phenotype correlations remain elusive. Brain MRI appears as a useful tool for genotype/phenotype correlations. Here, we summarise the various combinations of MRI lesions observed in the most frequent mitochondrial respiratory chain deficiencies so as to direct molecular genetic test in patients at risk of such diseases. We believe that the combination of brain MRI features is of value to support respiratory chain deficiency and direct molecular genetic tests.
Mitochondrial diseases are due to deficiency of the respiratory chain, which is made up of five complexes and consists of more than 80 different proteins. These diseases are characterised by a broad clinical and genetic heterogeneity that makes diagnosis difficult. Some clinical presentations are highly suggestive of given gene mutations, allowing rapid genetic diagnosis. However, owing to the wide pattern of symptoms in mitochondrial disorders and the constantly growing number of disease genes, their genetic diagnosis is frequently difficult and genotype/phenotype correlations remain elusive.
Here, based on brain MRI features in known nuclear/mitochondrial DNA mutations, we have tried to provide physicians with valuable information so as to help them in interpreting the growing amount of data derived from exome sequencing and targeted gene resequencing in mitochondrial diseases.
Based on the current review of published literature, we have focused our MRI analysis for the genotype/phenotype correlations on five brain areas known as targets of mitochondrial dysfunction: (1) basal ganglia (hyperintensities on T2-weighted imaging or calcifications); (2) cerebellum (hyperintensities on T2 or atrophy); (3) brainstem (hyperintensities on T2 or atrophy); (4) white matter (leucoencephalopathy); (5) cortex (supra-tentorial atrophy). Stroke-like episodes were also considered. The combination of some features and absence of others are sometimes suggestive of a particular respiratory chain deficiency or gene mutation. We believe that the combination of brain MRI anomalies is of value to support respiratory chain deficiency and interpret next-generation sequencing data in respiratory chain deficiency.
Abstract and Introduction
Abstract
Mitochondrial diseases are characterised by a broad clinical and genetic heterogeneity that makes diagnosis difficult. Owing to the wide pattern of symptoms in mitochondrial disorders and the constantly growing number of disease genes, their genetic diagnosis is difficult and genotype/phenotype correlations remain elusive. Brain MRI appears as a useful tool for genotype/phenotype correlations. Here, we summarise the various combinations of MRI lesions observed in the most frequent mitochondrial respiratory chain deficiencies so as to direct molecular genetic test in patients at risk of such diseases. We believe that the combination of brain MRI features is of value to support respiratory chain deficiency and direct molecular genetic tests.
Introduction
Mitochondrial diseases are due to deficiency of the respiratory chain, which is made up of five complexes and consists of more than 80 different proteins. These diseases are characterised by a broad clinical and genetic heterogeneity that makes diagnosis difficult. Some clinical presentations are highly suggestive of given gene mutations, allowing rapid genetic diagnosis. However, owing to the wide pattern of symptoms in mitochondrial disorders and the constantly growing number of disease genes, their genetic diagnosis is frequently difficult and genotype/phenotype correlations remain elusive.
Here, based on brain MRI features in known nuclear/mitochondrial DNA mutations, we have tried to provide physicians with valuable information so as to help them in interpreting the growing amount of data derived from exome sequencing and targeted gene resequencing in mitochondrial diseases.
Based on the current review of published literature, we have focused our MRI analysis for the genotype/phenotype correlations on five brain areas known as targets of mitochondrial dysfunction: (1) basal ganglia (hyperintensities on T2-weighted imaging or calcifications); (2) cerebellum (hyperintensities on T2 or atrophy); (3) brainstem (hyperintensities on T2 or atrophy); (4) white matter (leucoencephalopathy); (5) cortex (supra-tentorial atrophy). Stroke-like episodes were also considered. The combination of some features and absence of others are sometimes suggestive of a particular respiratory chain deficiency or gene mutation. We believe that the combination of brain MRI anomalies is of value to support respiratory chain deficiency and interpret next-generation sequencing data in respiratory chain deficiency.
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