Beware of Leigh Syndrome Pedigrees with MT-ATP6 Mutation Whose Primary Diagnosis is Retinitis Pigmentosa

Abstract

Abstract purpose: Maternally Inherited Leigh Syndrome (MILS) is a group of systemic diseases caused by defects in mitochondrial oxidative phosphorylation (OXPHOS). We aim to investigate the clinical and genetic characteristics of MILSpedigree with MT-ATP6 mutation who were first diagnosed with RP. Methods: This study included a family pedigree consisting of a proband with visual blurring symptoms, his mother with similar symptoms, and a father who was asymptomatic. The medical history was asked, and the best corrected visual acuity (BCVA), intraocular pressure, slit-lamp, wide-field fundus photography, optical coherence tomography (OCT), visual evoked potential (VEP) and whole exome sequencing were performed. In addition, brain Magnetic Resonance Imaging (MRI) and physical examination were performed for the mother and child. Results: Whole exon sequencing showed that the proband carried mitochondrial MT-ATP6 gene mutation. The proband's mother carried an 8993T>G heterozygous mutation, with a heterozygous mutation load of 86%, which was inherited from the proband's mother (heterozygous mutation load of 62%). This gene is the primary pathogenic gene of MILS. The patient was diagnosed with MILS after a complete physical examination and imaging examination. Conclusions: This study suggests that RP can be the cause of the first visit of MILS patients. Therefore, ophthalmologists should be alert to MILS when they find patients with clinical symptoms of the nervous system in the face of RP patients. MT-ATP6 mutation is one of the causes of RP, and its pathogenic mechanism has not been clearly explained. In the future, the research and intervention of MT-ATP6 mutation may provide a new direction for the diagnosis and treatment of MILS-related RP.