Bayrak Harun, Sezer Abdullah, Kılıç Mustafa
Division of Pediatric Metabolism, Dr. Sami Ulus Maternity and Child Health Training and Research Hospital, University of Health Sciences, Ankara, Turkey.
Department of Medical Genetics, Dr. Sami Ulus Maternity and Child Health Training and Research Hospital, University of Health Sciences, Ankara, Turkey.
Mol Syndromol. 2024 Dec;15(6):487-494. doi: 10.1159/000538930. Epub 2024 May 22.
Mutations in the RMND1 gene that cause defects in the mitochondrial respiratory chain result in a highly variable phenotypic presentation. The protein required for meiotic nuclear division 1 homolog (RMND1) is localized to the inner mitochondrial membrane and is encoded by the nuclear genome.
We report a new patient from a consanguineous family who was severely affected by a previously described combined oxidative phosphorylation deficiency 11 and was treated rapidly due to early diagnosis.
We also included patients with RMND1 mutation in the literature. We analyzed the epidemiological, clinical, laboratory, and genetic data of a total of 49 patients (98 alleles) in the literature, including our patient. We summarized all previously published patients and focused on the importance of early diagnosis.
The most common variant in patients with RMND1 mutation was c.713A>G (p.Asn238Ser). Mortality was significantly lower in patients with homozygous and compound heterozygous c.713A>G (p.Asn238Ser) mutations ( < 0.001). The second most common mutation was c1349G>C (p.450Serext31), which was reported in 11 patients (22.4%). Cardiac involvement and mortality were more common in patients with homozygous c.1349G>C (p.450Serext32) mutation ( = 0.008 and 0.008, respectively).
In this study, the effect of cardiac involvement on mortality in RMND1 mutation was shown for the first time. We reported that mortality was lower in the c.713A>G (p.Asn238Ser) mutation. Furthermore, mortality was more common in the c.1349G>C (p.450Serext32) mutation. These findings have not been previously reported in the literature. They are reported for the first time in this study.
RMND1基因的突变会导致线粒体呼吸链出现缺陷，从而导致高度可变的表型表现。减数分裂核分裂1同源物（RMND1）所需的蛋白质定位于线粒体内膜，由核基因组编码。
我们报告了一名来自近亲家庭的新患者，该患者受到先前描述的联合氧化磷酸化缺陷11的严重影响，并因早期诊断而得到及时治疗。
我们还纳入了文献中携带RMND1突变的患者。我们分析了包括我们的患者在内的文献中总共49名患者（98个等位基因）的流行病学、临床、实验室和遗传数据。我们总结了所有先前发表的患者，并强调了早期诊断的重要性。
RMND1突变患者中最常见的变体是c.713A>G（p.Asn238Ser）。纯合和复合杂合c.713A>G（p.Asn238Ser）突变患者的死亡率显著较低（<0.001）。第二常见的突变是c1349G>C（p.450Serext31），11名患者（22.4%）报告有该突变。纯合c.1349G>C（p.450Serext32）突变患者的心脏受累和死亡率更为常见（分别为=0.008和0.008）。
在本研究中，首次显示了心脏受累对RMND1突变患者死亡率的影响。我们报告c.713A>G（p.Asn238Ser）突变患者的死亡率较低。此外，c.1349G>C（p.450Serext32）突变患者的死亡率更为常见。这些发现以前在文献中未曾报道。它们在本研究中首次报告。
