鉴定线粒体疾病患者的致病RNU4-2变异:拓宽线粒体功能障碍的非编码RNA基因变异谱

IF 2.5 3区 生物学 Q2 GENETICS & HEREDITY
Kohta Nakamura, Yoshihito Kishita, Atsuko Imai-Okazaki, Taku Omata, Maki Nodera, Yukiko Yatsuka, Ayumu Sugiura, Naoyuki Matsumoto, Holger Prokisch, Hiroshi Matsumoto, Akira Ohtake, Kei Murayama, Yasushi Okazaki
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引用次数: 0

摘要

线粒体疾病的特征是由于线粒体功能障碍导致能量产生受损。尽管测序技术取得了进步,但许多病例仍然无法从基因上得到诊断。我们报告了两例线粒体疾病,在非编码RNA基因RNU4-2中具有相同的新生变异,先前与神经发育障碍相关。重新分析357例确定可能患有线粒体疾病的患者的全基因组测序数据(见方法:补充数据S1),确定了2例具有致病性RNU4-2变异(GRCh38: chr)。[12:12 . 29] [au:]NR_003137.2: n.64_65insT)。两例患者均表现为耗氧量下降,临床特征包括发育迟缓、小头畸形、身材矮小。这项研究提供了将RNU4-2变异与线粒体疾病联系起来的第一个证据,扩大了与该基因相关的表型谱。我们的研究结果强调了在线粒体疾病诊断中重新分析基因组数据和考虑非编码RNA基因变异的重要性,这可能会提高以前未解决病例的诊断。
本文章由计算机程序翻译,如有差异,请以英文原文为准。

Identification of a pathogenic RNU4-2 variant in patients with mitochondrial disease: Broadening the spectrum of non-coding RNA gene variants in mitochondrial dysfunction

Identification of a pathogenic RNU4-2 variant in patients with mitochondrial disease: Broadening the spectrum of non-coding RNA gene variants in mitochondrial dysfunction
Mitochondrial diseases are characterized by impaired energy production due to mitochondrial dysfunction. Despite advances in sequencing technologies, many cases remain genetically undiagnosed. We report two cases of mitochondrial disease harboring identical de novo variant in the non-coding RNA gene RNU4-2, previously associated with neurodevelopmental disorders. Re-analysis of whole genome sequencing data from 357 patients ascertained as possibly having mitochondrial disease (see Methods: Supplementary Data S1) identified two cases with a pathogenic RNU4-2 variant (GRCh38: chr.12:120291839: T > TA; NR_003137.2: n.64_65insT). Both patients exhibited decreased oxygen consumption rates and clinical features including developmental delay, microcephaly, short stature. This study provides the first evidence linking RNU4-2 variant to mitochondrial disease, expanding the phenotypic spectrum associated with this gene. Our findings highlight the importance of re-analyzing genomic data and considering non-coding RNA gene variants in mitochondrial disease diagnostics, potentially improving the diagnosis of previously unsolved cases.
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来源期刊
Journal of Human Genetics
Journal of Human Genetics 生物-遗传学
CiteScore
7.20
自引率
0.00%
发文量
101
审稿时长
4-8 weeks
期刊介绍: The Journal of Human Genetics is an international journal publishing articles on human genetics, including medical genetics and human genome analysis. It covers all aspects of human genetics, including molecular genetics, clinical genetics, behavioral genetics, immunogenetics, pharmacogenomics, population genetics, functional genomics, epigenetics, genetic counseling and gene therapy. Articles on the following areas are especially welcome: genetic factors of monogenic and complex disorders, genome-wide association studies, genetic epidemiology, cancer genetics, personal genomics, genotype-phenotype relationships and genome diversity.
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