Centre for Neuromuscular Disorders, Centre for Translational Neuro- and Behavioral Sciences, Department of Pediatric Neurology, University Duisburg-Essen, 45147 Essen, Germany.
Leibniz-Institut für Analytische Wissenschaften-ISAS e.V., 44139 Dortmund, Germany.
Int J Mol Sci. 2021 Jul 22;22(15):7835. doi: 10.3390/ijms22157835.
Mutations in the gene are associated with epilepsy, hearing loss and mental retardation syndrome (EHLMRS). While is ubiquitously expressed and is attributed a role within mitochondrial morphogenesis during spermatogenesis, there is only limited knowledge about the associated muscular and molecular pathology. This study reports on a comprehensive workup of muscular pathology, including proteomic profiling and microscopic studies, performed on an 8-year-old girl with typical clinical presentation of EHLMRS, where exome analysis revealed two clinically relevant, compound-heterozygous variants in . Proteomic profiling of a quadriceps biopsy showed the dysregulation of 82 proteins, out of which 15 were localized in the mitochondrion, while 19 were associated with diseases presenting with phenotypical overlap to EHLMRS. Histological staining of our patient's muscle biopsy hints towards mitochondrial pathology, while the identification of dysregulated proteins attested to the vulnerability of the cell beyond the mitochondria. Through our study we provide insights into the molecular etiology of EHLMRS and provide further evidence for a muscle pathology associated with SPATA5 deficiency, including a pathological histochemical pattern accompanied by dysregulated protein expression.
基因突变与癫痫、听力损失和智力迟钝综合征（EHLMRS）有关。虽然在精子发生过程中线粒体形态发生中具有普遍表达和作用，但对于相关的肌肉和分子病理学知之甚少。本研究报告了对肌肉病理学的全面检查，包括蛋白质组学分析和显微镜研究，对一名 8 岁女孩进行了典型的 EHLMRS 临床表型分析，外显子组分析显示在中存在两个具有临床意义的复合杂合变异体。股四头肌活检的蛋白质组学分析显示 82 种蛋白质失调，其中 15 种定位于线粒体，而 19 种与具有表型重叠的疾病相关。我们患者的肌肉活检组织化学染色提示存在线粒体病理学，而失调蛋白的鉴定证明了细胞除了线粒体之外的脆弱性。通过我们的研究，我们深入了解了 EHLMRS 的分子病因，并进一步证明了与 SPATA5 缺乏相关的肌肉病理学，包括伴随失调蛋白表达的病理组织化学模式。
