The ENG1 Leber's hereditary optic neuropathy (LHON) family spans six generations and comprises more than 90 maternally related individuals. In this pedigree, the G:A LHON mutation at nucleotide position 11778 shows a complex pattern of segregation in which it is homoplasmic mutant in two branches, homoplasmic wildtype in another, and heteroplasmic in a fourth branch. In addition, there is co-segregation of the 11778 mutant allele and of a G:A silent polymorphism at nucleotide position 5471 in 18 of 19 family members. This co-segregation indicates that the two substitutions arose either simultaneously, or nearly so, in the same "founder" mtDNA molecule. However, the highly divergent mitochondrial allele ratios in the one family member suggest that there has been a complex origin and segregation "history" of these two substitutions. Taking all of the results into consideration, the evidence supports sequential single mutations at sites 5471 and 11778, in close temporal proximity, with subsequent segregation of the intermediate mutational genotype to high levels in one branch of the ENG1 LHON family. In other branches, either the double wildtype or double mutant genotype has become essentially homoplasmic.
Download full-text PDF |
Source |
|---|---|
| http://dx.doi.org/10.1007/s00439-004-1203-x | DOI Listing |
Publication Analysis
Top Keywords
Similar Publications
LNC-ing Genetics in Mitochondrial Disease.
Noncoding RNA
November 2024
Department of Medicine, Division of Cardiology, University of Colorado Anschutz Medical Campus, Aurora, CO 80045, USA.
Primary mitochondrial disease (MD) is a group of rare genetic diseases reported to have a prevalence of 1:5000 and is currently without a cure. This group of diseases includes mitochondrial encephalopathy, lactic acidosis, and stroke-like episodes (MELAS), maternally inherited diabetes and deafness (MIDD), Leber's hereditary optic neuropathy (LHON), Leigh syndrome (LS), Kearns-Sayre syndrome (KSS), and myoclonic epilepsy and ragged-red fiber disease (MERRF). Additionally, secondary mitochondrial dysfunction has been implicated in the most common current causes of mortality and morbidity, including cardiovascular disease (CVD) and cancer.
View Article and Find Full Text PDFRespiratory Chain Complex I Deficiency in Leber Hereditary Optic Neuropathy: Insights from Ophthalmologic and Molecular Investigations in Tunisia.
BMC Genomics
November 2024
Research Laboratory of Human Genome and Multifactorial Diseases, Faculty of Pharmacy, University of Monastir, Street Avicenne, Monastir, 5000, Tunisia.
Background: Leber hereditary optic neuropathy (LHON) is a mitochondrial DNA (mtDNA) rare disease due to the pathogenic variant of the NADH dehydrogenase enzyme. LHON is characterized by a sudden central vision loss due to focal degeneration of the retinal ganglion cell layer and optic nerve. Symptoms usually appear between the age of 18 and 35 years.
View Article and Find Full Text PDFClinical and genetic landscape of optic atrophy in 826 families: insights from 50 nuclear genes.
Brain
October 2024
State Key Laboratory of Ophthalmology, Zhongshan Ophthalmic Center, Sun Yat-sen University, Guangdong Provincial Key Laboratory of Ophthalmology and Visual Science, Guangzhou 510060, China.
Hereditary optic neuropathies (HON) are a group of diseases due to genetic defects either in mitochondria or in nuclear genomes. The increasing availability of genetic testing has expanded a broader genetic and phenotypic spectrum of HON than previously recognized. To provide systematic insight into the genetic and phenotypic landscape of HON attributed to 50 nuclear genes, we conducted genetic analysis on part of 4776 index patients with clinical diagnosis of HON following our previous study on 1516 probands with Leber hereditary optic neuropathy (LHON) and mitochondrial DNA variants.
View Article and Find Full Text PDFMitochondrial tRNA 14693A > G Mutation, an "Enhancer" to the Phenotypic Expression of Leber's Hereditary Optic Neuropathy.
Adv Sci (Weinh)
November 2024
Center for Genetic Medicine, the Fourth Affiliated Hospital of School of Medicine, and International School of Medicine, International institutes of Medicine, Zhejiang University, Yiwu, 322000, China.
Article Synopsis
- Leber's hereditary optic neuropathy (LHON) is mainly caused by mutations in mitochondrial DNA and affects vision, with a specific focus on the impact of mitochondrial tRNA variants.
- The study explores two particular mutations, tRNA 14693A > G and ND6 14484T > C, in families from China affected by LHON, revealing how they influence mitochondrial function and cell stress responses.
- The findings suggest that mitochondrial tRNA mutations may increase autophagy, while mutations in mitochondrial protein genes lead to apoptosis, highlighting the complex interaction of these genetic factors in LHON.
Want AI Summaries of new PubMed Abstracts delivered to your In-box?
Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!