Clinico-pathological and Molecular Spectrum of Mitochondrial Polymerase γ Mutations in a Cohort from India.

Autor: Deepha S; Department of Neuropathology, National Institute of Mental Health and Neurosciences (NIMHANS), Bangalore, India.; Neuromuscular Laboratory, Neurobiology Research Centre (NRC), National Institute of Mental Health and Neurosciences (NIMHANS), Bangalore, India., Govindaraj P; Department of Neuropathology, National Institute of Mental Health and Neurosciences (NIMHANS), Bangalore, India.; Neuromuscular Laboratory, Neurobiology Research Centre (NRC), National Institute of Mental Health and Neurosciences (NIMHANS), Bangalore, India.; Institute of Bioinformatics, International Tech Park, Bangalore, India.; Manipal Academy of Higher Education, Manipal, India., Sankaran BP; Neuromuscular Laboratory, Neurobiology Research Centre (NRC), National Institute of Mental Health and Neurosciences (NIMHANS), Bangalore, India.; Department of Neurology, National Institute of Mental Health and Neurosciences (NIMHANS), Bangalore, India.; Genetic Metabolic Disorders Service, Children's Hospital at Westmead, Sydney, NSW, Australia., Chiplunkar S; Neuromuscular Laboratory, Neurobiology Research Centre (NRC), National Institute of Mental Health and Neurosciences (NIMHANS), Bangalore, India.; Department of Clinical Neurosciences, National Institute of Mental Health and Neurosciences (NIMHANS), Bangalore, India., Kashinkunti C; Department of Neurology, National Institute of Mental Health and Neurosciences (NIMHANS), Bangalore, India., Nunia V; CSIR-Centre for Cellular and Molecular Biology, Hyderabad, India.; Radiation & Cancer Biology Laboratory, Department of Zoology, University of Rajasthan, Jaipur, India., Nagappa M; Neuromuscular Laboratory, Neurobiology Research Centre (NRC), National Institute of Mental Health and Neurosciences (NIMHANS), Bangalore, India.; Department of Neurology, National Institute of Mental Health and Neurosciences (NIMHANS), Bangalore, India., Sinha S; Department of Neurology, National Institute of Mental Health and Neurosciences (NIMHANS), Bangalore, India., Khanna T; Indian Council of Medical Research (ICMR), New Delhi, India., Thangaraj K; CSIR-Centre for Cellular and Molecular Biology, Hyderabad, India.; Centre for DNA Fingerprinting and Diagnostics, Hyderabad, India., Taly AB; Neuromuscular Laboratory, Neurobiology Research Centre (NRC), National Institute of Mental Health and Neurosciences (NIMHANS), Bangalore, India.; Department of Neurology, National Institute of Mental Health and Neurosciences (NIMHANS), Bangalore, India., Gayathri N; Department of Neuropathology, National Institute of Mental Health and Neurosciences (NIMHANS), Bangalore, India. gayathri.narayanappa@gmail.com.; Neuromuscular Laboratory, Neurobiology Research Centre (NRC), National Institute of Mental Health and Neurosciences (NIMHANS), Bangalore, India. gayathri.narayanappa@gmail.com.
Jazyk: angličtina
Zdroj: Journal of molecular neuroscience : MN [J Mol Neurosci] 2021 Nov; Vol. 71 (11), pp. 2219-2228. Date of Electronic Publication: 2021 Jan 19.
DOI: 10.1007/s12031-020-01765-8
Abstrakt: Polymerase γ catalytic subunit (POLG), a nuclear gene, encodes the enzyme responsible for mitochondrial DNA (mtDNA) replication. POLG mutations are a major cause of inherited mitochondrial diseases. They present with varied phenotypes, age of onset, and severity. Reports on POLG mutations from India are limited. Hence, this study aimed to describe the clinico-pathological and molecular observations of POLG mutations. A total of 446 patients with clinical diagnosis of mitochondrial disorders were sequenced for all exons and intron-exon boundaries of POLG. Of these, 19 (4.26%) patients (M:F: 10:9) had POLG mutations. The age of onset ranged from 5 to 55 years with an overlapping phenotypic spectrum. Ptosis, peripheral neuropathy, seizures, and ataxia were the common neurological features observed. The most common clinical phenotype was chronic progressive external ophthalmoplegia (CPEO) and CPEO plus (n = 14). Muscle biopsy showed characteristic features of mitochondrial myopathy in fourteen patients (14/19) and respiratory chain enzyme deficiency in eleven patients (11/19). Multiple mtDNA deletions were seen in 47.36% (9/19) patients. Eight pathogenic POLG variations including two novel variations (p.G132R and p.V1106A) were identified. The common pathogenic mutation identified was p.L304R, being present in eight patients (42.1%) predominantly in the younger age group followed by p.W748S in four patients (21%). To the best of our knowledge, this is the first extensive study from India, highlights the clinico-pathological and molecular spectrum of POLG mutations.
(© 2021. Springer Science+Business Media, LLC, part of Springer Nature.)
Databáze: MEDLINE
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