Paramasivam, A;
Venkatapathi, C;
Sandeep, G;
Meena, AK;
Uppin, MS;
Mohapatra, S;
Pitceathly, RDS;
(2019)
Homozygous R627W mutations in POLG cause mitochondrial DNA depletion leading to encephalopathy, seizures and stroke-like episodes.
Mitochondrion
, 48
pp. 78-83.
10.1016/j.mito.2019.08.003.
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Pitceathly_Homozygous R627W mutations in POLG cause mitochondrial DNA depletion leading to encephalopathy, seizures and stroke-like episodes_AAM.pdf - Accepted Version Download (5MB) | Preview |
Abstract
Mutations in the mitochondrial DNA maintenance gene POLG (DNA Polymerase Gamma, Catalytic Subunit), encoding mitochondrial DNA polymerase gamma (pol γ), are associated with an extremely broad phenotypic spectrum. We identified homozygous POLG c.1879C>T; p.R627W mutations in two siblings from a consanguineous South Asian family following targeted resequencing of 75 nuclear-encoded mitochondrial genes. Both patients presented with encephalopathy, seizures and stroke-like episodes, and mitochondrial DNA depletion was confirmed in the proband's muscle tissue. Subsequent Sanger sequencing of POLG in a further 275 unrelated probands with genetically unconfirmed mitochondrial disease revealed a third unrelated proband with a similar phenotype harboring homozygous c.1879C>T; p.R627W mutations and a fourth patient, with a milder clinical disorder, harboring compound heterozygous POLG c.1879C>T; p.R627W and c.2341G>A; p.A781T mutations. Given endogamous practices in the Indian subcontinent, homozygous POLG c.1879C>T; p.R627W mutations should be excluded in South Asian patients presenting with encephalopathy, seizures and stroke-like episodes.
| Type: | Article |
|---|---|
| Title: | Homozygous R627W mutations in POLG cause mitochondrial DNA depletion leading to encephalopathy, seizures and stroke-like episodes |
| Location: | Netherlands |
| Open access status: | An open access version is available from UCL Discovery |
| DOI: | 10.1016/j.mito.2019.08.003 |
| Publisher version: | https://doi.org/10.1016/j.mito.2019.08.003 |
| Language: | English |
| Additional information: | This version is the author accepted manuscript. For information on re-use, please refer to the publisher’s terms and conditions. |
| Keywords: | Mitochondrial disease, POLG, Encephalopathy, Seizures, Status Epilepticus, Stroke-like episode, mtDNA |
| UCL classification: | UCL UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Brain Sciences UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Brain Sciences > UCL Queen Square Institute of Neurology UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Brain Sciences > UCL Queen Square Institute of Neurology > Department of Neuromuscular Diseases |
| URI: | https://discovery.ucl.ac.uk/id/eprint/10080576 |
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