Mitochondrial Complex 1 Deficiency

[Hutan]

A member with the symptoms of severe ME/CFS along with some swallowing issues had their genome sequenced by Sequencing.com.

This is the report on one of the variants found:

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High Evidence
Mitochondrial Complex 1 Deficiency, Nuclear Type 1

Genetic variants detected for this condition
Variant ID rs 754873418, RCV005419177
Evidence: High
Risk Status: Likely carrier

Gene NDUFV2
Gene information: NDUFV2, also known as NADH: ubiquinone oxidoreductase core subunit V2, is a gene that provides instructions for making a protein that is a crucial component of Complex 1, the first major enzyme complex in the mitochondria that powers our cells. This protein helps convert nutrients into usable energy through a process called cellular respiration. Mutations in the NDUF2 gene can lead to mitochondrial disorders, which are rare genetic conditions characterised by muscle weakness, neurological problems, and other complications because cells cannot produce enough energy to function properly. these disorders typically appear in infancy or early childhood and can affect multiple organ systems especially those with high energy demand such as the brain, muscles, heart and liver.

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We note the 'Likely carrier' status, but, given the person's symptoms, it seems sensible to consider if this finding could account for them. The member hasn't had their mitochondrial genome sequenced.

We are interested in your thoughts about this.

 

[Jonathan Edwards]

Gene NDUFV2

It would probably be legitimate to check whether any signal has come up for this gene in the genetic studies of ME/CFS to date, including DecodeME or the Snyder study?

A nuclear (as opposed to mitochondrial) DNA segment would be expected to produce disease in early childhood if acting alone. But it is conceivable that having a gene mutation might make the course of ME/CFS worse or make the difference between having it or not, I guess.

 

[Hutan]

Link to the Genecard entry for NDUFV2

And here's the Malacard - link

A form of mitochondrial complex I deficiency, the most common biochemical signature of mitochondrial disorders, a group of highly heterogeneous conditions characterized by defective oxidative phosphorylation, which collectively affects 1 in 5-10000 live births. Clinical disorders have variable severity, ranging from lethal neonatal disease to adult-onset neurodegenerative disorders. Phenotypes include macrocephaly with progressive leukodystrophy, non- specific encephalopathy, cardiomyopathy, myopathy, liver disease, Leigh syndrome, Leber hereditary optic neuropathy, and some forms of Parkinson disease. MC1DN7 transmission pattern is consistent with autosomal recessive inheritance.

Disease Ontology
A nuclear type mitochondrial complex I deficiency that has material basis in homozygous or compound heterozygous mutation in the NDUFV2 gene on chromosome 18p11.22.

 

[forestglip]

It would probably be legitimate to check whether any signal has come up for this gene in the genetic studies of ME/CFS to date, including DecodeME

Nothing much in DecodeME. Maybe a single variant downstream of the gene with a p-value of 1e-4: https://my.locuszoom.org/gwas/894183/region/?chrom=18&start=8963196&end=9250245

 

[forestglip]

Genetic variants detected for this condition
Variant ID rs 754873418, RCV005419177
Evidence: High
Risk Status: Likely carrier

ClinVar page for this variant: https://www.ncbi.nlm.nih.gov/clinvar/variation/1194462/

 

[forestglip]

the Snyder study?

It's not ranked highly at all in the Zhang preprint. It's ranked 14287. The lower the number, the more relevant the gene was considered.

 

[mariovitali]

I wonder how this patient feels if given Flavin Mononucleotide (FMN)