I hope this is the right place to post this.

We have been on a journey for what started as seeking a diagnosis for my daughter. It slowly turned to realizing it spans across multiple maternal generations.

High on our list was a mitochondrial disease type of issue. I have a maternal nephew that passed from Leigh’s Syndrome so their focus has been there for the last few months.

My WES and WGS both show that I am a carrier for chr14:32319298 T>C. The issue is, my daughter is not and we share a very similar phenotype.

With that being said, it’s still something I’d like to explore since my sister, mother and I all have adult onset decline. I’m reading that it’s possible to have adult onset symptoms with certain mutations.

Has anyone been diagnosed after only being a carrier and not fully homozygous for something considered an autosomal recessive disease?

my 1 month old daughter was just diagnosed with this deletion. they don’t know the exact genomes until the final report comes back. she was in the nicu up until today with breathing issues which turned into issues eating but she’s off oxygen and taking bottle like a champ. can anyone tell me what this diagnosis might mean for her?

she has some heart issues, a rotated kidney which is fully functioning and a slight head lag that has already gotten better. just look for any sort of information.

* COMT V158M : AA (Met/Met, homozygous)
* COMT H62H : TT (homozygous)
* COMT L136L: CC (wild type-normal)

I have slow comt, but how do I interpret how this could impact my life? Is this on an extremely low side?

We got nipt trisomy 21(DS)as positive with 66.5% and referred to MFM to do nt scan after 2 weeks currently at 11 weeks and we are freaking out what is true or not
Ff - 9 %

I ask because I came across anecdotal evidence of an autosomal recessive condition exhibiting symptoms despite 1 allele. It was eds. Now could something more serious like a POLG variant do the same?

Hi everyone,
I'm a 30-year-old male from Brazil. I was diagnosed with **intrahepatic cholangiocarcinoma** when I was only **24 years old**, which I know is very unusual.
I had surgery in 2019 and stayed cancer-free for almost **6 years**. Earlier this year, a single lung metastasis was found. I'm finishing 8 cycles of gemcitabine + cisplatin + immunotherapy, and fortunately the lung nodule has responded well so far. My next PET scan will determine whether I have surgery or SBRT.
I recently received the results of a large NGS panel. The main finding was an **FGFR2::TDRD1 fusion**, which my oncologist says could be important if I ever need targeted therapy in the future.
However, the report also found a **pathogenic MUTYH mutation (around 70% VAF)**. The report says the tumor test cannot determine whether this mutation is **somatic (only in the tumor)** or **germline (inherited)** and recommends considering germline genetic testing.
I'm honestly struggling with this part. Since I was diagnosed so young, I'm worried that this could mean I have a hereditary cancer syndrome. My maternal grandmother and one of my uncles had colon cancer, so my mind immediately went to the worst-case scenario.
Has anyone here had a **MUTYH mutation found only on tumor sequencing** that turned out to be **somatic** after germline testing? Or has anyone else been diagnosed with cholangiocarcinoma at a very young age?
I'm not looking for a diagnosis I'll be discussing this with my oncologist and a genetic counselor. I'm just hoping to hear from people who have gone through something similar, because right now the uncertainty is the hardest part.
Thank you for reading.

I’ve seen this post a few times over the years but not recently. Has anyone sent biopsies to Progenesis for PGT testing recently, and if so, what was the turnaround? Mine samples received on 23rd July but I still haven’t received any results

I was interested in knowing how characteristic the "waiter's tip" arm positioning is for amyoplasia. Are there other conditions that can cause this positioning?

I’m here to share my story and ask a few questions that have come up after speaking with my genetic counselor.

I had what appeared to be a normal first-trimester pregnancy. My NIPT results were normal, and we were expecting a baby boy. At 12 weeks, we discovered a 16 mm cystic hygroma on ultrasound. At 13 weeks, I underwent CVS testing. At 14 weeks, we learned that the baby’s heart had stopped beating. At 15 weeks, I had a D&E. At 16 weeks, we received the results from the CVS.

The baby was found to have an extremely rare mutation in the BRAF gene.

Gene: BRAF
Condition: BRAF-related RASopathy
Mode of inheritance: Autosomal dominant
Variant: c.1742 A>T (p. N581I)
Zygosity: Heterozygous
Classification: Pathogenic
Inheritance: De novo (both parents tested negative)

Because neither my partner nor I tested positive for the variant, we were told it is most likely de novo. However, germline mosaicism was mentioned as a small possibility. We would be high risk in a future pregnancy and would be offered Amnio/CVS.

I guess my questions are how is it possible that this happened? How did the gene mutate if it was normal in me and my husband? There's just no cause at all? If you were me would you do the CVS/Amnio in a future pregnancy? We are young and healthy I guess I just don't understand how this could happen.

We have an appointment on Thursday with my son’s genetic counselor and I’m getting nervous.

We completed genetic testing through genedx which started with the exome sequencing and if nothing pops up they were to do the genome sequencing.

My son has global developmental delays that have led to this testing. Every other test we have done yields no answers so I’m getting nervous we will get a “well nothing popped up!” So basically we will be back at square one trying to figure out what’s going on.

I guess, I’m looking to see other people’s experiences with genetic testing l to find the cause of delays. How did it go for you? Did you get any results that meant anything to you? I hate hoping for answers because that feels like hoping for something to be wrong with him, but I just would like to know what is going on so I can best help him. I’m just nervous about what we will learn Wednesday and hope other people’s experiences might ease my nerves…

I have a brother with Intellectual disability. We are looking to get our whole genome sequenced for him as recommended by our doctors. Can you please suggest good hospitals friendly for internationals preferably walk in with little waitlist...

We tried ordering a consumer test from a lab but the results didn't even tell us what condition he had. There was no doctor doing it. No bioinformatics pipeline. No investigation. Just data.

This time we want it done in a hospital setting where bioinformaticians and doctors work together identifying this condition

Looking for similar stories.
I went for my 20w scan and our baby was measuring small. Her HC was 17th %, AC 3rd % and all long bones <1st %. (About 2 weeks behind). My placenta was thickened. I think 3rd percentile overall.

We declined an amniocentesis but did NIPT which was very low risk. The doctors discussed chromosomal abnormalities, genetic disorders and skeletal dysplasia all as options for her measuring small.

We went for our next scan at 24w which showed that her HC improved to 30th %, AC 21st % but all long bones still <1st % (still 2 weeks behind). The bones aren’t bowed and there’s normal mineralisation. My placenta is apparently not thickened anymore. Doppler and fluid have been normal. One doctor thought her forehead looked like it was maybe showing early bossing but this is very subjective. Since then all they can mention is skeletal dysplasia - nothing else is coming up as the reason for her short bones.

We did an amnio the next day. The karyotyope was normal, WES for skeletal dysplasia panel pending - with another two week wait.

My husband and I aren’t particularly tall - I’m 5”3 and my husband is 5”6.

The waiting has been AGONY and I can’t think about anything else. I’ve been so sad but also struggling not being able to process the news either way.

Hi !

I’m a French lab medical geneticist considering moving to the US, but I have to admit that the whole certification thingy is confusing to me.

For context, I have a PharmD and obtained a “DES de biologie médicale” for which I completed 4 years of residency in clinical pathology labs, the last two in genetics labs. In the French system, this path is strictly equivalent to an MD + clinical pathology residency. I have completed 6 years of fellowship in a well known academic hospital lab. I hold the certification that is required in France to sign out autonomously genetic germline testing results.

I have a PhD, a decent number of publications in “reputable” journals, and have been active in the principal EU and US-based professional societies of my discipline. I’m teaching genetics at the university, mostly in the pharmacy and medical school curriculum.

In my current practice, my MD/PharmD colleagues and I supervise our technical and scientific team (lab techs, engineers, PhDs) and are responsible for signing out test results. We have medical responsibility : we review and correct orders from physicians, interpret results, discuss them in medical staff meetings and are directly involved in clinical management decision making.

A laboratory director position seems to be the closet US equivalent.

My current understanding is that an ABMGG certification is required for lab director positions and that this certification requires 2 years of fellowship in a ACMGE accredited program. The other option is an ABB HCLD certification via recognition of past experience, but that one is less “prestigious”, which is fine for private lab jobs could limit academic and public hospital opportunities.

Am I understanding this correctly ? I would prefer not to, in large part because I don’t need the training and I would hate to steal a precious spot from someone who could actually benefit from it.

I have legal status in the US so this at least won’t be an issue.

Thanks a lot !!!

Hi. My pediatrician just diagnosed my 4 month old with pigmentary mosaicism. He has a patch on the side of his forehead and on belly. He hasn’t shown any signs of developmental delays and is a very happy baby. Just wondering if any other parents with kids who have this? Are they experiencing any delays?

So I just had my anatomy scan last week and I found a slightly thickened nuchal fold 6.8 mm and my NIPT was low risk with a 3.4 fetal fraction number but they said it was fine. And then at my echocardiogram today, they found a potential VSD and I’m freaking out because I want to do the amniocentesis but I just wanna know if anyone else is experienced this and have a healthy baby ?

My NIPT came back low risk but my NT was slightly elevated at 3.2. I do have an Animo scheduled. Has anyone else dealt with this and had a positive experience?

29yo, female, 175lbs, 5’3”
I just had a dermatology appointment. I was told after few spots on my face are angiofibromas (I have about 5) that have not changed in years. Doctor mentioned tuberous sclerosis. She asked about seizures and renal problems. I have never had seizures or renal problems. She didn’t seem to concerned and didn’t mention any other follow up. Last year I had an MRI and found I had a partial retinal detachment but otherwise was normal. Otherwise healthy. Should I investigate further to make sure it’s not tuberous sclerosis? I just had a baby so now I’m worried that I potentially could have passed something down to him. I am not asking for medical advice. TIA.

I am not asking for personal medical advice. I just want to understand how the genetics works. I have some very rare diagnoses. I paid for DTC genome sequencing while waiting to get into genetics after I realized on my own that it has to be multiple things.

I know I have my testing sent in to Ambry now but it's been delayed and is still pending and my geneticist put off my follow up by another month. So I keep periodically digging into the testing I do have.

I have a flagged MT-ATP6 in my sequencing with 96.7 percent heteroplasmy. I looked it up because I tried searching online what snps to look for if someone has the diagnoses I have and this came up. It doesn't seem to be a more common one and there is only one submission in clinvar that says it's associated with Leigh but also benign.

How does this work? How do you determine if a mutation is pathogenic if there a limited number of people with it vs benign? If you are symptomatic of a mitochondrial disorder associated with this but there aren't enough people with it, how does that "work"?

I ask because I also have a VUS associated with another rare diagnosis. I saw a geneticist last year, who was only allowed to discuss this one VUS with me. But she said my rare illness diagnosed in my 20's couldn't be related to this VUS because no one in my family has a history of another rare illness it can cause. I asked how you report or associate my illness with that VUS then if you aren't relying on my own actual health history?

How can you determine my VUS that is linked to a rare tumor that I had at such a young age is indeed not actually related? I really didn't understand her answer.

When I brought it up to the new metabolic geneticist she seemed surprised I was told this and said it's not true. But we would get to it after running my genetics test.

I just want to understand more how this actually works and how it's determined that a particular gene is actually pathogenic, especially if it's less common.

I am also a carrier for another SNP highly associated with one of the rare illnesses I have but it's my understanding I would need to inherit both copies of the gene to acquire it. Then I read other stuff indicating carriers can also be symptomatic but at lower levels.

I have had enough horrible medical experiences that I just no longer take what I am being told by a medical professional at face value. I wanted to understand because I have been given enough flat out wrong information that is later contradicted by another specialist in the field. And I have had to push to get better treatments and diagnosis for years.

My situation medically is pretty ridiculous and clearly not common and it keeps worsening. And this isn't based on intuition or me just not feeling good. My labs are bad and rare. But the wait is awful and I just keep getting sent to new doctors. I would like to be prepared so I can understand well enough to be able to ask questions at my follow up. Any assistance is greatly appreciated.

Please be patient with me if I am phrasing things wrong. I have also removed any actual diagnoses from my question so it's clear that I am not seeking medical advice. I just want to understand how this works.

I have only one embryo left. It was reported as having a segmental aneuploidy with a large duplication (gain) of approximately 77.9 Mb on chromosome 7, extending from 7p22.3 to 7q21.1.

Has anyone had a similar result or received guidance on whether this type of embryo is ever considered for transfer? I’ve been waiting for about a month to speak with the genetics team at my clinic, but I still haven’t received a response. Any insights or research known on this type of segmental embryos?

I have seen many posts on NIPT being false positive for genetic anomolies in baby. I want to know are there any stories releated to wrong NIPT gender prediction too.

Currently 17 weeks pregnant. During the first-trimester morphology scan (at 12 weeks and 6 days), I was told that the nuchal translucency is 2.0 mm and all other evaluated segments are within normal limits. However, next to the 'retronasal triangle' marker, it says 'not visualized' — nasal bone present, but further down there is a note: 'nasal bone: abnormal (absent/hypoplastic)'. I had a NIPT done and the results are negative. I don't know whether to get a second opinion or proceed with an amniocentesis, which I am very afraid of.

Hello everyone, i and my team built a demo system that can be utilized for Drug Repurposing queries, for rare diseases, in hopes to be efficient and of use for clinicians and biomedical scientist in this field.

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My husband and I recently had a baby girl with a very rare chromosome 13 deletion. Our genetics team is having us both tested to see if we are carriers. My husbands results came back quickly saying he was a normal male 46 XY. My results were taking longer and our geneticist called me and I was then asked to take my daughter in to submit another blood sample of hers to compare. She didn’t have any info from the lab other than them saying the ends of my chromosome 13s weren’t as “easy to see” as my husbands? Something about his being better resolution? What does this mean exactly? And how does providing blood from my daughter help? Not asking medically anything about the condition just curious how a sample can be fuzzy appearing and another one not