The frequency of mitochondrial polymerase gamma related disorders in a large Polish population cohort.

Dorota Piekutowska-Abramczuk, Magdalena Kaliszewska, Anna Sułek, Natalia Jurkowska, Mariusz Ołtarzewski, Ewa Jabłońska, Joanna Trubicka, Aleksandra Głowacka, Elżbieta Ciara, Paweł Kowalski, Karolina Langiewicz-Wojciechowska, Marketa Tesarova, Jiri Zeman, Biruta Kierdaszuk, Dariusz Kuczyński, Dariusz Chmielewski, Edyta Szymańska, Agnieszka Bakuła, Anna Łusakowska, Marta Lipowska, Bogdan Brodacki, Joanna Pera, Małgorzata Dorobek, Małgorzata Rydzanicz, Rafał Płoski, Krystyna Halina Chrzanowska, Ewa Bartnik, Grzegorz Placha, Anna Kamińska, Anna Kostera-Pruszczyk, Małgorzata Krajewska-Walasek, Katarzyna Tońska, Ewa Pronicka

Journal: Mitochondrion 2020;47():179-187

PMID: 30423451

Full Text on Elsevier Science View on PubMed

Abstract

Diseases related to DNA polymerase gamma dysfunction comprise of heterogeneous clinical presentations with variable severity and age of onset. Molecular screening for the common POLG variants: p.Ala467Thr, p.Trp748Ser, p.Gly848Ser, and p.Tre251Ile has been conducted in a large population cohort (n = 3123) and in a clinically heterogeneous group of 1289 patients. Recessive pathogenic variants, including six novel ones were revealed in 22/26 patients. Infantile Alpers-Huttenlocher syndrome and adulthood ataxia spectrum were the most common found in our group. Distinct molecular profile identified in the Polish patients with significant predominance of p.Trp748Ser variant (50% of mutant alleles) reflected strikingly low population frequency of the three remaining variants and slightly higher p.Trp748Ser allele frequency in the general Polish population as compared to the non-Finish European population.

Address: Department of Medical Genetics, The Children's Memorial Health Institute, Al. Dzieci Polskich 20, 04-730 Warsaw, Poland. Electronic address: [email protected].; Institute of Genetics and Biotechnology, Faculty of Biology, University of Warsaw, Pawinskiego 5a, 02-106 Warsaw, Poland.; Department of Genetics, Institute of Psychiatry and Neurology, Sobieskiego 9, 02-957 Warsaw, Poland.; Department of Medical Genetics, The Children's Memorial Health Institute, Al. Dzieci Polskich 20, 04-730 Warsaw, Poland.; Screening Tests Department, Institute of Mother and Child, Kasprzaka 17a, 01-211 Warsaw, Poland.; Department of Pediatrics and Adolescent Medicine, First Faculty of Medicine, Charles University and General University Hospital in Prague, Ke Karlovu 455/2, 128 08 Prague 2, Czech Republic.; Department of Neurology, Medical University of Warsaw, Banacha 1a, 02-097 Warsaw, Poland.; Department of Neurology and Epileptology, The Children's Memorial Health Institute, Al. Dzieci Polskich 20, 04-730 Warsaw, Poland.; Department of Pediatrics, Nutrition and Metabolic Disorders, The Children's Memorial Health Institute, Al. Dzieci Polskich 20, 04-730 Warsaw, Poland.; Department of Gastroenterology, Hepatology, Feeding Disorders and Pediatrics, The Children's Memorial Health Institute, Al. Dzieci Polskich 20, 04-730 Warsaw, Poland.; Clinic of Neurology, Military Institute of Medicine, Szaserow 128, 04-349 Warsaw, Poland.; Department of Neurology, Jagiellonian University Medical College, Botaniczna 3, 31-503 Krakow, Poland.; Department of Neurology, Central Clinical Hospital of the Ministry of Interior in Warsaw, Woloska 137, 02-507 Warsaw, Poland.; Department of Medical Genetics, Warsaw Medical University, Pawinskiego 3c, 02-106 Warsaw, Poland.; Institute of Genetics and Biotechnology, Faculty of Biology, University of Warsaw, Pawinskiego 5a, 02-106 Warsaw, Poland; Institute of Biochemistry and Biophysics, Polish Academy of Sciences, Pawinskiego 5a, 02-106 Warsaw, Poland.; Department of Internal Medicine, Hypertension, and Vascular Diseases, Medical University of Warsaw, Banacha 1a, 02-097 Warsaw, Poland.; Department of Medical Genetics, The Children's Memorial Health Institute, Al. Dzieci Polskich 20, 04-730 Warsaw, Poland; Department of Pediatrics, Nutrition and Metabolic Disorders, The Children's Memorial Health Institute, Al. Dzieci Polskich 20, 04-730 Warsaw, Poland.

DOI: 10.1016/j.mito.2018.11.004

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MeSH Terms: Adolescent, Adult, Amino Acid Substitution, Ataxia, Child, Child, Preschool, DNA Polymerase gamma, Diffuse Cerebral Sclerosis of Schilder, Female, Genes, Recessive, Humans, Infant, Infant, Newborn, Male, Middle Aged, Mitochondrial Diseases, Mutation, Missense, Poland