与 Leigh 综合征相关的复合杂合 MRPS14 变体

Compound Heterozygous MRPS14 Variants Associated With Leigh Syndrome.

作者信息

Otero Maria Gabriela, Freeman Christina, Shah Ruchi, Bai Renkui, Cui Hong, Castro Marian, Myers Zachary, Choy Eric, Chan Derek, Easter Molly, Zhao Sophia Y, Babros Madeline, Garg Ruchi, Deardorff Matthew, Moser Franklin, Pierson Tyler Mark

机构信息

Board of Governors Regenerative Medicine Institute, Cedars-Sinai Medical Center, Los Angeles, California, USA.

Biomedical Sciences, Cedars-Sinai Medical Center, Los Angeles, California, USA.

出版信息

Ann Clin Transl Neurol. 2025 May 2;12(8):1693-7. doi: 10.1002/acn3.70065.

DOI:10.1002/acn3.70065

PMID:40317698

原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC12343306/

Abstract

MRPS14 (uS14m) is a nuclear-encoded ribosomal protein important for mitochondria-specific translation. To date, only a single individual with a recessive MRPS14-related disorder (also known as COXPD38) has been reported. We report an additional subject possessing novel compound heterozygous MRPS14 variants (p.Asp37Asn, p.Asn60Asp). The subject presented at 2 years with motor and language delays associated with elevated serum lactate/alanine levels. Brain MRI showed a constellation of signal abnormalities consistent with Leigh Syndrome, while MR spectroscopy had an increased lactate peak. Western blots of fibroblasts showed decreased MRPS14 and COX2 protein levels. These results support the pathogenicity of the MRPS14 variants identified here.

摘要

MRPS14（uS14m）是一种对线粒体特异性翻译很重要的核编码核糖体蛋白。迄今为止，仅报道了一名患有隐性MRPS14相关疾病（也称为COXPD38）的个体。我们报告了另一名具有新型复合杂合MRPS14变体（p.Asp37Asn，p.Asn60Asp）的受试者。该受试者在2岁时出现运动和语言发育迟缓，伴有血清乳酸/丙氨酸水平升高。脑部MRI显示一系列与 Leigh 综合征一致的信号异常，而磁共振波谱显示乳酸峰升高。成纤维细胞的蛋白质免疫印迹显示MRPS14和COX2蛋白水平降低。这些结果支持此处鉴定的MRPS14变体的致病性。