Title |
Genetic diversity of NDUFV1-dependent mitochondrial complex I deficiency
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Published in |
European Journal of Human Genetics, July 2018
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DOI | 10.1038/s41431-018-0209-0 |
Pubmed ID | |
Authors |
Anshika Srivastava, Kinshuk Raj Srivastava, Malavika Hebbar, Chelna Galada, Rajagopal Kadavigrere, Fengyun Su, Xuhong Cao, Arul M. Chinnaiyan, Katta M. Girisha, Anju Shukla, Stephanie L. Bielas |
Abstract |
Medical genomics research performed in diverse population facilitates a better understanding of the genetic basis of developmental disorders, with regional implications for community genetics. Autosomal recessive mitochondrial complex I deficiency (MCID) accounts for a constellation of clinical features, including encephalopathies, myopathies, and Leigh Syndrome. Using whole-exome sequencing, we identified biallelic missense variants in NDUFV1 that encodes the 51-kD subunit of complex I (NADH dehydrogenase) NDUFV1. Mapping the variants on published crystal structures of mitochondrial complex I demonstrate that the novel c.1118T > C (p.(Phe373Ser)) variant is predicted to diminish the affinity of the active pocket of NDUFV1 for FMN that correlates to an early onset of debilitating MCID symptoms. The c.1156C > T (p.(Arg386Cys)) variant is predicted to alter electron shuttling required for energy production and correlate to a disease onset in childhood. NDUFV1 c.1156C > T (p.(Arg386Cys)) represents a founder variant in South Asian populations that have value in prioritizing this variant in a population-specific manner for genetic diagnostic evaluation. In conclusion, our results demonstrate the advantage of analyzing population-specific sequences to understand the disease pathophysiology and prevalence of inherited risk variants in the underrepresented populations. |
X Demographics
Geographical breakdown
Country | Count | As % |
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Sweden | 1 | 50% |
Unknown | 1 | 50% |
Demographic breakdown
Type | Count | As % |
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Members of the public | 2 | 100% |
Mendeley readers
Geographical breakdown
Country | Count | As % |
---|---|---|
Unknown | 31 | 100% |
Demographic breakdown
Readers by professional status | Count | As % |
---|---|---|
Researcher | 7 | 23% |
Student > Doctoral Student | 2 | 6% |
Unspecified | 2 | 6% |
Student > Bachelor | 2 | 6% |
Professor | 2 | 6% |
Other | 4 | 13% |
Unknown | 12 | 39% |
Readers by discipline | Count | As % |
---|---|---|
Biochemistry, Genetics and Molecular Biology | 8 | 26% |
Medicine and Dentistry | 3 | 10% |
Agricultural and Biological Sciences | 3 | 10% |
Unspecified | 2 | 6% |
Pharmacology, Toxicology and Pharmaceutical Science | 1 | 3% |
Other | 1 | 3% |
Unknown | 13 | 42% |