학술논문
The frequency of mitochondrial polymerase gamma related disorders in a large Polish population cohort.
Document Type
Article
Author
Piekutowska-Abramczuk, Dorota; Kaliszewska, Magdalena; Sułek, Anna; Jurkowska, Natalia; Ołtarzewski, Mariusz; Jabłońska, Ewa; Trubicka, Joanna; Głowacka, Aleksandra; Ciara, Elżbieta; Kowalski, Paweł; Langiewicz-Wojciechowska, Karolina; Tesarova, Marketa; Zeman, Jiri; Kierdaszuk, Biruta; Kuczyński, Dariusz; Chmielewski, Dariusz; Szymańska, Edyta; Bakuła, Agnieszka; Łusakowska, Anna; Lipowska, Marta
Source
Subject
*DNA polymerases
*INFANT diseases
*POPULATION
*GENE frequency
*AGE of onset
*
*
*
*
Language
ISSN
1567-7249
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. • AHS is the most frequent presentation of POLG disease in infants and young children. • POLG mutations are relatively rare cause of neurological involvement in adults (ANS and PEO). • Cerebellar syndrome, sensory-motor neuropathy, ophthalmoplegia and multiple mtDNA deletions justify POLG mutations searching. • Predominant p.Trp748Ser variant accounts for 50% of mutated alleles in the Polish patients. [ABSTRACT FROM AUTHOR]