Expanding the Clinical and Genetic Features Associated with Combined Oxidative Phosphorylation Deficiency 11 Short Title: RMND1 Overview: A case report and review of the literatures

Abstract

Mutations in the RMND1 gene that cause defects in the mitochondrial respiratory chain result in a very variable phenotypic clinic. We present a new patient from a consanguineous family who was severely affected by a previously identified combined oxidative phosphorylation deficiency 11 and was treated promptly due to early diagnosis. At the 24th hour of her birth, she did not pass the cardiac pulse oximetry screening and presented with significant plasma creatinine and lactic acid elevation in laboratory findings. This case is the first patient of Turkish origin reported in the literature. RMND1-related mitochondrial disease was described for the first time in a patient who failed the neonatal cardiac examination. We also included patients with RMND1 mutation in the literature. Up-to-date, forty-eight patients have been reported. We analyzed the epidemiological, clinical, laboratory, and genetic data of 49 patients (98 alleles). We summarized all previously published patients and focus on the importance of early diagnosis. The most common variant in patients with RMND1 mutation was c.713A > G (p.Asn238Ser). Mortality was statistically significantly lower in patients with homozygous and compound heterozygous c.713A > G (p.Asn238Ser) mutations (p:<0.001). The second most common mutation was c1349G > C (p.*450Serext*31) and was reported in 11 patients (22.4%). Cardiac involvement and mortality were more common in patients with homozygous c.1349G > C (p.*450Serext*32) mutation (p:0.008 and 0.008 respectively). In this study, the effect of cardiac involvement on mortality in RMND1 mutation has been shown for the first time. We reported that mortality was lower in the c.713A > G (p.Asn238Ser) mutation. Additionally, mortality was more common in the c.1349G > C (p.*450Serext*32) mutation. These findings have not been previously reported in the literature.