Expanding the Genetic and Phenotypic Spectrum of POLRMT-Related Mitochondrial Disease.

IF 2.3 3区医学 Q2 GENETICS & HEREDITY

Clinical Genetics Pub Date : 2025-06-29 DOI:10.1111/cge.70011

Mahmoud R Fassad, Sebastian Valenzuela, Monika Oláhová, Jack J Collier, Charlotte V Y Knowles, Eleni Mavraki, Miriam Elbracht, Nergis Güzel, Thomas Herberhold, Ingo Kurth, Andrea Maier, Larissa Mattern, Carol Saunders, Helen McCullagh, Katrin Õunap, Saskia B Wortmann, Andre Reis, Lei Zhang, Claes M Gustafsson, Robert McFarland, Robert W Taylor

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引用次数: 0

Abstract

Mitochondrial diseases are a complex group of conditions exhibiting significant phenotypic and genetic heterogeneity. Genomic testing is increasingly used as the first step in the diagnostic pathway for mitochondrial diseases. We used next-generation sequencing followed by bioinformatic data analysis to identify potentially damaging variants in the POLRMT gene (NM_005035.4) in six new affected individuals. Structural protein analysis predicted the detrimental impact of variants on POLRMT protein structure. Patients show extended phenotypic abnormalities often presenting early in life with features including global developmental delay, cognitive impairment, short stature and muscular hypotonia. This study expands the genetic and phenotypic landscape of mitochondrial disease associated with POLRMT variants.

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扩大polrmt相关线粒体疾病的遗传和表型谱。

线粒体疾病是一组复杂的病症，表现出显著的表型和遗传异质性。基因组检测越来越多地被用作线粒体疾病诊断途径的第一步。我们使用下一代测序和生物信息学数据分析，在6个新的受影响个体中鉴定出POLRMT基因（NM_005035.4）的潜在破坏性变异。结构蛋白分析预测了变异对POLRMT蛋白结构的有害影响。患者表现出延长的表型异常，通常在生命早期表现出整体发育迟缓、认知障碍、身材矮小和肌肉张力低下等特征。这项研究扩展了与POLRMT变异相关的线粒体疾病的遗传和表型景观。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Clinical Genetics 医学-遗传学

CiteScore

6.50

自引率

0.00%

发文量

175

审稿时长

3-8 weeks

期刊介绍： Clinical Genetics links research to the clinic, translating advances in our understanding of the molecular basis of genetic disease for the practising clinical geneticist. The journal publishes high quality research papers, short reports, reviews and mini-reviews that connect medical genetics research with clinical practice. Topics of particular interest are: • Linking genetic variations to disease • Genome rearrangements and disease • Epigenetics and disease • The translation of genotype to phenotype • Genetics of complex disease • Management/intervention of genetic diseases • Novel therapies for genetic diseases • Developmental biology, as it relates to clinical genetics • Social science research on the psychological and behavioural aspects of living with or being at risk of genetic disease