A new pathogenic POLG variant

S Nicholas Russo; Ekta G Shah; William C Copeland; Mary Kay Koenig

doi:10.1016/j.ymgmr.2022.100890

A new pathogenic POLG variant

Mol Genet Metab Rep. 2022 Jul 12:32:100890. doi: 10.1016/j.ymgmr.2022.100890. eCollection 2022 Sep.

Authors

S Nicholas Russo^{1

2}, Ekta G Shah¹, William C Copeland³, Mary Kay Koenig^{1

2}

Affiliations

¹ The University of Texas McGovern Medical School, Department of Pediatrics, Division of Child and Adolescent Neurology, Houston, TX, USA.
² Center for the Treatment of Pediatric Neurodegenerative Disease, The University of Texas McGovern Medical School, Houston, TX, United States of America.
³ Mitochondrial DNA Replication Group, Genome Integrity and Structural Biology Laboratory, National Institute of Health, Research Triangle Park, NC, USA.

Abstract

POLG gene mutations are the most common causes of inherited mitochondrial disorders. The enzyme produced by this gene is responsible for the replication and repair of mitochondrial DNA. To date, around 300 pathogenic variants have been described in this gene. The resulting clinical outcomes of POLG mutations are widely variable in both phenotype and severity. There is considerable overlap in the phenotype of the so-called POLG syndromes with no clear genotype-phenotype correlation. Here we describe a newly discovered pathogenic variant in the POLG gene in a 7-year-old male that died of uncontrollable refractory status epilepticus. Genetic epilepsy panel sequencing identified two variants in the POLG gene, the common p.A467T pathological mutation and a novel p.S809R POLG variant found in trans with the p.A467T POLG that accompanied a severely reduced mitochondrial DNA level in the patient's tissues.

Keywords: Alpers-Huttenlocher syndrome; DNA polymerase gamma; Mitochondria; Mitochondrial depletion; POLG syndrome.

Publication types

Case Reports