İlknur Erol, Leman Tekin Orgun, Şeyda Beşen, Elif Perihan Öncel, İbrahim Boğa, Atıl Bişgin, Özlem Alkan

Objectives RMND1 protein belongs to a large mitochondrial inner membrane complex that supports translation of the mtDNA-encoded polypeptides. Mutations in the RMND1 gene have recently been linked to infantile onset mitochondrial disease characterised by multiple mitochondrial respiratory chain defects named as combined oxidative phosphorylation defect 11(COXPD11).The clinical phenotypes are expanding from a fatal infantile encephalomyopathy with lactic acidosis to a less severe phenotype characterised by developmental delay,congenital sensorineural deafness,hypotonia and renal disease. Methods Herein,we present two siblings with a novel homozygous mutation in RMND1 gene. Results A 11-year-old girl who is the first child of healthy and consanguineous parents presented with refractory seizures, developmental delay and congenital hearing loss at 7 years old. Her brother and cousins had also developmental delay and hearing loss. Physical examination revealed autistic features with spasticity. All metabolic analysis other than increased plasma lactate level were normal. EEG was consistent with active multifocal epileptic abnormality. Although the brain MRI showed symmetrical signal increase in bilateral lentiform nuclei, MR spectroscopy was normal. While karyotype and microarray analysis were normal, whole exome sequencing identified a novel homozygous c.791T>A (p.V264E) mutation in RMND1 gene(NM_017909.4). Same homozygous mutation was detected in her 8 year-old brother with heterozygous mutation in her parent s and sister. Conclusion Herein, we described two siblings with a novel homozygous mutation of RMND1 gene with severe neurologic phenotype without renal involvement.

Keywords: COXPD11,RMND1,homozygous,oxidative phosphorylation

İlknur Erol
Baskent University Faculty of Medicine, Adana Dr. Turgut Noyan Application and Research Center
Turkey

Leman Tekin Orgun
Baskent University Faculty of Medicine, Adana Dr. Turgut Noyan Application and Research Center
Turkey

Şeyda Beşen
Baskent University Faculty of Medicine, Adana Dr. Turgut Noyan Application and Research Center
Turkey

Elif Perihan Öncel
Baskent University Faculty of Medicine, Adana Dr. Turgut Noyan Application and Research Center
Turkey

İbrahim Boğa
Cukurova University AGENTEM (Adana Genetic Diseases Diagnosis and Treatment Center) and Medical Genetics Department of Medical Faculty
Turkey

Atıl Bişgin
Cukurova University AGENTEM (Adana Genetic Diseases Diagnosis and Treatment Center) and Medical Genetics Department of Medical Faculty
Turkey

Özlem Alkan
Baskent University Faculty of Medicine, Adana Dr. Turgut Noyan Application and Research Center
Turkey