波兰大人群队列中线粒体聚合酶γ相关疾病的频率。

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

机构信息

Department of Medical Genetics, The Children's Memorial Health Institute, Al. Dzieci Polskich 20, 04-730 Warsaw, Poland.

Institute of Genetics and Biotechnology, Faculty of Biology, University of Warsaw, Pawinskiego 5a, 02-106 Warsaw, Poland.

出版信息

Mitochondrion. 2019 Jul;47:179-187. doi: 10.1016/j.mito.2018.11.004. Epub 2018 Nov 10.

DOI:10.1016/j.mito.2018.11.004

PMID:30423451

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.

摘要

与 DNA 聚合酶 γ 功能障碍相关的疾病具有不同的临床表现，严重程度和发病年龄各不相同。已经对一个大型人群队列（n=3123）和一个临床异质性的 1289 名患者组进行了常见 POLG 变异体：p.Ala467Thr、p.Trp748Ser、p.Gly848Ser 和 p.Tre251Ile 的分子筛查。在 26 名患者中的 22 名发现了隐性致病性变异体，包括六个新变异体。我们的研究组中最常见的是婴儿期 Alpers-Huttenlocher 综合征和成年期共济失调谱系。在波兰患者中发现的独特分子谱显著以 p.Trp748Ser 变异体为主（50%的突变等位基因），与非芬兰欧洲人群相比，这反映了其余三种变异体的人群频率明显较低，而 p.Trp748Ser 等位基因频率略高。