Genetic testing?

Around the time that I was seeing a geneticist for other reasons, I asked my ENT about genetic testing. She mentioned that some hearing loss is syndromic but most is not.

I was diagnosed with a mitochondrial disease by the geneticist through genetic testing. Hearing loss is associated with many mitochondrial diseases including mine although mitochondrial diseases are much more heterogenous in presentation than other genetic diseases.

Ah, my cinderblocks are so obviously due to my family’s genetics that it was a NO-BRAINER.

I get my sensorineuraly-challenged ears from father’s side. His dad passed along cinderblocks to my dad, who passed them along to me. Ironically (or maybe not) my mom had age-related hearing loss that she passed along to my sister - both in their mid-to-late 40s when they needed aids.

If anyone is interested in genetic testing but you want to save $1000’s of dollars this is what I found out.
My wife had breast cancer about 8 years ago. she had to get some genetic tests and that cost us about $5500. then I had high iron and I had to get genetic tests (hemochromatosis) for liver issues. another about $3500.
After all this I signed myself and my wife up on 23andme for their Health and ancestry service (their best package).
When we received our results, at first I just looked at everything, but after a while it dawned on me to check 23and me results against our flagrantly expensive hospital tests.
I was shocked (and sickened) to see that the results were exactly the same. IDENTICAL!
It cost me $5500 for having only a couple of genes tested for my wife and $3500 for a couple of genes for me!!!
What a scam.
24and me gave us genetic test results on literally hundreds of genes. They give you the results if they find you have the gene and if it is likely or highly likely or concerning , etc. And they still send me emails notifying me of updates when new genes are determined to be linked to health problems.
And it didn’t even cost $200 bucks.
I have results on hundreds of genes and here is a real kicker.
I mentioned this to every doctor and they all said the same thing. If I had the 23and me results they accept them. the hospitals accept them. They are recognized just the same as if they came from any medical lab. I found out The FDA even recognizes 23and me results.
Every gene the hospitals tested for me and my wife were also in the 23and me results, and they had the same information, the same probabilities and so on.
Here are a couple of pictures of a few of my own gene test notices. 23anddme goes into a lot of detail if you want to drill down on your results.

OH if you are interested then 23and me sometimes offers a discount on the Health and ancestry deal. right now it is only $148 but the offer expires on the 16th. but they have the offer a few times a year.
I think that this genetic testing is one of the smartest things you can do to help yourself based on my experiences and knowledge.
good for you and everyone in your family.

And there is a whole lot more. this is only a tiny bit of the info they give on just one of my genes.

I haven’t had the test, but I have read that my hearing loss type is simplimatic of a genetic hearing loss, but it also is common with my military service of flying in and being around jet engines and aircraft without hearing protection. I am rated as being 50% disabled by the VA for my severe hearing loss, and the fact my word recognition scores are more in line with a profound loss. Now my word recognition has improved due to therapy sessions.

If I was to be tested, some time down the line, I also envision that the piece of information that could be potentially useful is how much of my low frequency hearing is likely to be remain over time (my ski-slope is slowly moving to the left).

This open-access paper nicely reviews causes of hearing loss:

Hearing Loss in Adults1

Genetics is a frequent cause but may involve one of a large set of genes, moreover some conspire with environmental factors (incomplete penetration). The nice thing about 23andMe is indeed that you get raw, reliable data for tens of thousands of SNPs (single nucleotide polymorphisms, those rs numbers). I am not sure the company software will flag all the risks, so you may need to do some homework here… What “helps” is that many are autosomally dominant (affecting a parent and every sibling).

My own handicap probably relates to a massive dose of ototoxic antibiotics I got as a toddler, six decades ago in a “Third World” country (today’s NGO euphemism is “Low- and middle-income country”). Not blaming anyone, as I had a pretty serious infection and am unsure about the alternatives.

it’s funny really. we were looking at what is wrong with my mom so they had to test me first.
guess what? I have 6 genetic mutations. (one is the cause of my hearing loss which is HOMER2)
but get this: some of the mutations are from my mom and I know 2 that affects the heart is from my dad.

Did you find out that there were certain genes related to hearing loss and if so would you please share with me which they are? I am a 23&me customer. thanks

Note that late-onset hearing loss may both have environmental and genetic components (e.g. you might have a higher susceptibility for loud sounds)- just to complicate things further…

The other thing is that geneticists usually refer to “variants” rather than “mutations” (except for major deletions and the like). Our genome is a compromise for whatever suited our ancestors best in their lifetime (remember that none of yours died childless), and quite often “disease” variants are beneficial in a different context. This happens mostly in immunology with, for instance, genes that cause allergies (sometimes deadly, think peanuts) have probably protected our ancestors from even deadlier pathogens in the past. Ditto for genes associated with fast/slow blood clotting, and “funny personalities”. Just to say, do not feel inferior for whatever 23andMe flags.

Just for fun, I had my DNA tested recently. Below is an account of my experience.

I chose MyHeritageDNA for the analysis; it is cheap, I paid about 40 USD. The Company correctly put me on the map in the western provinces of Holland, with great precision. But if you are from European descent in the US, and your ancestors merrily interbred with other immigrants for centuries you will probably get mapped all over the European continent. Likewise, my wife’s messy DNA maps on three continents. You can also use MHD to get into touch with individuals who share your DNA (have not gone into this). Given humanity’s tendency to wander, one wonders what “ancestry” actually means. You can upload your raw data (more on this below) to another company, appropriately named MyTrueAncestry, which will map you to archeological remains going back to the Bronze Age (for free)—very interesting. I learned there we Dutch have mostly Viking roots.

But I also wanted to get some medical information. Sadly, companies are not allowed to provide this in most countries. The official reason is not to upset you with information the authorities feel you cannot handle, but I suspect this is really to avoid you screw life insurance companies and the like. Luckily, almost all companies do give you your raw data. This is not your actual 6-billion-letter DNA code but the next best thing: a list of half a million or so “SNPs”, single-nucleotide polymorphisms, points in the code known to differ between human populations. Most of these are non-coding (for proteins), but many of them do change the expression of such genes, or they are linked to more relevant DNA changes nearby. The SNPs are listed as rs-codes, followed by the unit (base) at that position in your DNA. This is given by two letters (e.g. AG, CC or CT), because, remember, each of your chromosomes comes in duplicates, one from your pa and one from your ma (the exception, in men, is the XY pair), 2 x 23 pairs in total. Since the human genome was decoded over two decades ago, many of those SNPs have been associated with medical conditions. Note that “associated” varies from near-certain fates (like Huntington’s disease) to a range of other, sometimes fuzzy conditions that are also affected by other loci and environmental effects. Some findings are widely accepted, other were made from a simple report, or have been retracted—so be aware this is a mixed bag.

Now what you can do is upload your data to companies that will sort out these things for you and come with recommendations (like: "eat your greens”, or note that you are likely to have freckles). Most of these are hazy and expensive reports, and even lack a citation of sources. One that seems quite good, though, is Promethease. Their USD 12 Report is a bit user-unfriendly, but its top items are “things of interest”, based on unusual findings and how well-established they are. They also provide details with links to a major SNP database and the source publications.

So near the top of my list came rs11090865(T;T), which is fairly rare (1.5% frequency). Combination of this genotype with rs267606617(G) (or mtDNA A1555G, one I luckily do not have), gives you prelingual profound deafness. But rs11090865T, in the TRMU gene, is still not great; “[change in] TRMU expression increases the sensitivity of hair-cell-like HEI-OC-1 cells to neomycin damage in vitro ”. Neomycin is an aminoglycoside antibiotic, in the same family as kanamycin, gentamycin and streptomycin, which are widely used, and well known to be ototoxic (causing deafness). So, in summary, I probably carry a genotype that makes me unusually susceptible to antibiotic-induced hearing loss. In fact, this is a very common cause of deafness (PMC5651232)—one paper I saw says that these antibiotics cause 50,000 hearing loss cases annually (Prevalence of aminoglycoside-induced hearing loss in drug-resistant tuberculosis patients: A systematic review - PubMed). However, they are also life-saving drugs, so no easy avoidance.

To understand what is going on here you need to know how these antibiotics work (sorry, getting a bit technical here). They target the protein translation machinery in bacteria. Now, we humans carry in all of our cells tiny “organs” called mitochondria. These burn sugars, spitting out energy-rich small molecules (ATP) that are used elsewhere in the cells to “fuel” all kind of reactions. Mitochondria are somewhat shaped like bacteria, with their own membrane, and there is a good reason for that resemblance; they merged long, long ago in evolution to form the eukaryotic cell (these also got a nucleus, with DNA). Now, the funny thing is that those mitochondria partly kept their bacterial DNA and protein-synthesizing machinery (ribosomes). So, for most of us, the biochemistry of our mitochondrial is sufficiently different from bacteria for antibiotics to be selective. But in some, the drugs will also kill hair cells. Why only hair cells? I don’t know. Perhaps they lack protection from the blood-brain-barrier, which keeps our brain mostly safe from nasty chemicals (and, sadly, useful drugs).

So I thought that was quite interesting, however, if I had to do it again, I would probably pick 23andMe for genotyping (as discussed above). They are a bit more expensive but cover far many more medically relevant SNPs that Promethease can work with. Also, most SNPs associated with hearing loss ( https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6457651/ ) are missing here. Finally, they don’t even genotype mitochondrial DNA, and your Y-chromosome (if you are male).

@ronshere what I don’t understand is why you had to have a genetic test for hemochromatosis. I had a simple blood test at a pathology clinic for this hemochromatosis. This blood test told me if I have the disease, don’t have the disease or I was a carrier. Turns out I’m a carrier. This blood test cost me $95 Aus.

How interesting. It is suspected that my mom’s cinderblocks for ears were passed along to me. Because I have the same symptoms that she does from time to time, including: fluid in the ears reducing my hearing, etc.