Category: LHON

Mitochondrial DNA Pathogenic Variant Prevalence in Primary Mitochondrial Disease Patients With African (L) Mitochondrial Genome Haplogroups

Primary mitochondrial diseases (PMD) are caused by pathogenic variants in over 350 genes, 37 of which are located in mitochondrial DNA (mtDNA). While more than 100 mtDNA variants have confirmed disease associations, there are few reports of mtDNA-related PMD in patients with African heritage, even in well-studied populations. We investigated the frequency of pathogenic mtDNA variants in African L-haplogroups in patients with confirmed PMD from two diagnostic cohorts. Data from genetically…

Leber’s hereditary optic neuropathy-associated ND1 3733G> C mutation ameliorates the mitochondrial quality control and cellular homeostasis

Leber’s hereditary optic neuropathy (LHON) is a paradigm for mitochondrial retinopathy due to mitochondrial DNA (mtDNA) mutations. However, the mechanism underlying LHON-linked mtDNA mutations, especially their impact on mitochondrial and cellular integrity, is not well understood. Recently, the ND1 3733G>C (p.E143Q) mutation was identified in three Chinese pedigrees with suggestively maternal inheritance of LHON. In this study, we investigated the pathogenic mechanism of m.3733G>C mutation…

Optic nerve MRI findings in Leber’s hereditary optic neuropathy

CONCLUSION: MRI lesions can extend from the intraorbital optic nerve to the chiasm and tract. Consistent with previous reports, chiasmal involvement was frequently observed and was more prevalent in younger patients. Recognition of these characteristic MRI and clinical findings is crucial in the differential diagnosis of subacute progressive optic neuropathy.

Early-Onset Hearing Loss in Leber’s Hereditary Optic Neuropathy: A Case Report

Leber hereditary optic neuropathy (LHON) is one of the most common mitochondrial disorders that is characterized in young adults and teenagers as bilateral, painless, subacute visual failure. Extraocular manifestations include neurological and cardiac features. Sensorineural hearing loss (SNHL) has not been reported as a clinical feature of this disorder. We report a patient diagnosed with LHON having the common m.11778G>A; p. Arg340 pathogenic variant who was also diagnosed with bilateral…

Nitric Oxide may Adversely Affect the Metabolism and Viability of Retinal Organoids Derived from Patients with Leber Hereditary Optic Neuropathy

Leber hereditary optic neuropathy (LHON) is a bilateral optic neuropathy associated with mitochondrial DNA (mtDNA) mutations characterized by parapapillary telangiectasia during the acute phase. However, its precise mechanism remains unclear. This study evaluated the effects of nitric oxide (NO) on retinal organoids (ROs) generated from induced pluripotent stem (iPS) cells derived from patients with LHON. Established iPS cells from three patients with the m.11778G>A mutation (patient group) and…

Exploring the Phenotypic Heterogeneity and Bioenergetic Profile of the m.13513G>A mtDNA Substitution: A Heteroplasmy Perspective

The m.13513G>A (p.Asp393Asn) substitution in the MT-ND5 (Mitochondrially Encoded NADH/Ubiquinone Oxidoreductase Core Subunit 5) gene is a common pathogenic variant associated with primary mitochondrial disorders. It frequently causes Leigh syndrome and mitochondrial encephalomyopathy with lactate acidosis and stroke-like episodes (MELAS). In this study, we present clinical data, heteroplasmy levels in various tissues (blood, urine, and skin fibroblasts), and bioenergetic characteristics from a…

Literature Commentary

In this issue of JNO, Drs. Mark L. Moster, Marc J. Dinkin, and Deborah I. Friedman discuss the following 6 articles:Piehl F, Eriksson-Dufva A, Budzianowska A, Feresiadou A, Hansson W, Hietala MA, Håkansson I, Johansson R, Jons D, Kmezic I, Lindberg C, Lindh J, Lundin F, Nygren I, Punga AR, Press R, Samuelsson K, Sundström P, Wickberg O, Brauner S, Frisell T. Efficacy and safety of rituximab for new-onset generalized myasthenia gravis: the RINOMAX randomized clinical trial. JAMA Neurol….

The crossroads of Leber hereditary optic neuropathy and autosomal dominant optic Atrophy: Clinical profiles of patients with coexisting pathogenic genetic variants

CONCLUSION AND IMPORTANCE: Mitochondrial optic neuropathies, which result in loss of retinal ganglion cells, are a substantial cause of visual impairment. Herein, we report two cases of combined LHON- and ADOA-causing pathogenic variants in two brothers, in addition to the genetic and ophthalmologic profile of their parents and two sisters.