+ Site Statistics
References:
54,258,434
Abstracts:
29,560,870
PMIDs:
28,072,757
+ Search Articles
+ Subscribe to Site Feeds
Most Shared
PDF Full Text
+ PDF Full Text
Request PDF Full Text
+ Follow Us
Follow on Facebook
Follow on Twitter
Follow on LinkedIn
+ Translate
+ Recently Requested

Severe infantile leigh syndrome associated with a rare mitochondrial ND6 mutation, m.14487T>C



Severe infantile leigh syndrome associated with a rare mitochondrial ND6 mutation, m.14487T>C



American Journal of Medical Genetics. Part a 161a(8): 2020-2023



We describe a case of severe infantile-onset complex I deficiency in association with an apparent de novo near-homoplasmic mutation (m.14487T>C) in the mitochondrial ND6 gene, which was previously associated with Leigh syndrome and other neurological disorders. The mutation was near-homoplasmic in muscle by NextGen sequencing (99.4% mutant), homoplasmic in muscle by Sanger sequencing, and it was associated with a severe complex I deficiency in both muscle and fibroblasts. This supports previous data regarding Leigh syndrome being on the severe end of a phenotypic spectrum including progressive myoclonic epilepsy, childhood-onset dystonia, bilateral striatal necrosis, and optic atrophy, depending on the proportion of mutant heteroplasmy. While the mother in all previously reported cases was heteroplasmic, the mother and brother of this case were homoplasmic for the wild-type, m.14487T. Importantly, the current data demonstrate the potential for cases of mutations that were previously reported to be homoplasmic by Sanger sequencing to be less homoplasmic by NextGen sequencing. This case underscores the importance of considering mitochondrial DNA mutations in families with a negative family history, even in offspring of those who have tested negative for a specific mtDNA mutation.

(PDF emailed within 0-6 h: $19.90)

Accession: 055739791

Download citation: RISBibTeXText

PMID: 23813926

DOI: 10.1002/ajmg.a.36000


Related references

Introducing the human Leigh syndrome mutation T9176G into Saccharomyces cerevisiae mitochondrial DNA leads to severe defects in the incorporation of Atp6p into the ATP synthase and in the mitochondrial morphology. Human Molecular Genetics 18(15): 2889-2898, 2009

A new mitochondrial DNA mutation in ND3 gene causing severe Leigh syndrome with early lethality. Pediatric Research 55(5): 842-846, 2004

G8363A mitochondrial DNA mutation is not a rare cause of Leigh syndrome - clinical, biochemical and pathological study of an affected child. Folia Neuropathologica 45(4): 187-191, 2008

Two mtDNA mutations 14487T>C (M63V, ND6) and 12297T>C (tRNA Leu) in a Leigh syndrome family. Molecular Genetics and Metabolism 96(2): 59-65, 2008

Progressive myoclonic epilepsy as an adult-onset manifestation of Leigh syndrome due to m.14487T>C. Journal of Neurology, Neurosurgery, and Psychiatry 81(1): 90-93, 2010

Confirmation that a T-to-C mutation at 9176 in mitochondrial DNA is an additional candidate mutation for Leigh's syndrome. Neuromuscular Disorders 8(3-4): 149-151, 1998

Novel mitochondrial C15620A variant may modulate the phenotype of mitochondrial G11778A mutation in a Chinese family with Leigh syndrome. Neuromolecular Medicine 16(1): 119-126, 2014

Adult leigh syndrome with mitochondrial DNA mutation at 8993--mutation ratio analysis on formalin-fixed autopsy tissues. Rinsho Shinkeigaku 41(2-3): 157, 2001

Mitochondrial DNA mutation and Leigh's syndrome. Annals of Neurology 32(4): 597-598, 1992

Mitochondrial DNA mutation 14487T>C manifesting as Leber's hereditary optic neuropathy. Journal of Neurology 262(12): 2776-2779, 2016

Novel mitochondrial mutation in the ND4 gene associated with Leigh syndrome. Acta Neurologica Scandinavica 114(5): 350-353, 2006

Novel mutation in mitochondrial DNA in 2 siblings with Leigh syndrome. Neurology. Genetics 2(5): E99, 2016

Infantile mitochondrial hepatopathy is a cardinal feature of MEGDEL syndrome (3-methylglutaconic aciduria type IV with sensorineural deafness, encephalopathy and Leigh-like syndrome) caused by novel mutations in SERAC1. American Journal of Medical Genetics. Part a 161a(9): 2204-2215, 2014

Adult Leigh syndrome with mitochondrial DNA mutation at 8993. Acta Neuropathologica 97(4): 416-422, April, 1999

A T-->C mutation at nt 8993 of mitochondrial DNA in a child with Leigh syndrome. Neurology 44(5): 972-974, 1994