A typical phenotypes due to NDUFV1 mutations


Nurun Nahar Borna and Yasushi Okazaki*

Mitochondria have a critical role in energy metabolism, generating and scavenging of free radicals, intracellular Ca2+ regulation, and cell mitophagy. Dysfunction of the mitochondrial oxidative phosphorylation complex is the most frequent inborn errors of metabolism. Mitochondrial diseases are highly diverse in etiology, age of the disease onset, involvement of multiple organ systems, and genetic causes. NDUFV1 is a core subunit of mitochondrial Complex I (CI), and mutations cause CI deficiency. Clinically, CI deficiency is associated with severe infantile lactic acidosis, cardiomyopathy, encephalomyopathy, leukoencephalopathy, and Leigh syndrome. The cellular biology and molecular mechanisms of mitochondrial diseases are still elusive due to the heterogeneous genetic background and lack of phenotype-genotype correlation. Neurological abnormalities are the second most frequent presentations of mitochondrial diseases, including white matter abnormalities, psychomotor regression, and mental disability. The defects in myelin sheath or glial cells cause leukodystrophy which is a progressive genetical syndrome. To date, no therapy is available to cure mitochondrial diseases; exploration of the phenotype and molecular background are crucial for disease diagnosis, supportive treatments, proper genetic counselling, prenatal diagnosis, and experimental treatments. This article underscores the atypical clinical presentations of NDUFV1 mutations and the importance of a multidisciplinary approach to correlate phenotypes, biochemical, radiological, and molecular diagnosis. Implementation of multidisciplinary approach will enhance the possibility of discovering the therapeutic targets to treat mitochondrial disorders and ensure prenatal diagnosis to prevent inherited diseases.


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