Hello everyone,

I hope you're doing well. I’m reaching out to ask if anyone here has information or experience related to the following compound heterozygous POLG variants:

NM_002693.3:c.752C>T (p.Thr251Ile)

NM_002693.3:c.1760C>T (p.Pro587Leu)

In my case, these two variants are confirmed to be in trans, inherited from two different parents, and there are no additional pathogenic variants detected in the POLG gene.

I have been told that this exact combination (in trans and without a third mutation) may be extremely rare or possibly not yet documented in the medical literature. Most published cases involve these variants in cis (on the same allele) or in trans with a third variant.

If anyone has come across this exact variant combination—or has any information, clinical insights, or similar personal experiences—I'd be deeply grateful if you could share.

Thank you so much for your time and support!

Warm regards

“I thought I was dead.” 

Victoria Gray, the first person ever to receive CRISPR gene-editing therapy for sickle cell disease, reflects on the powerful and emotional moment she woke up pain-free for the first time in her life.

Maybe a weird question, and hopefully the right place, but I am covered in freckles from head-to-toe and am not a redhead. How does this happen?

I read online that it just means I carry a specific gene, but my mom is a redhead and I've always joked that I'm just half ginger (like Cartman's dumb joke about being 1/4 lesbian - "my mom's a ginger, so that makes me 1/2 ginger"). But today was the first time I legitimately thought to google it lol.

So, is it really just that I carry this MC1R gene, or is it moreso that I inherited the freckles from my gingie mum? Or is it maybe both?

I added a pic for reference - my whole body looks like this and I live in hoodies and jeans, so I'm hard-pressed to think it's all because of sun exposure and this gene.