u/orbitolinid

Ich brauche neue Wanderschuhe. Ich suche Schuhe in 40.5, maennlich. In meinem Wohnort gibt es nur einen Sportladen, der Maennerschuhe erst ab 42 anbietet. Frauenschuhe sind zu schmal und die Geometrie stimmt einfach nicht. Fuer ab und zu mal eine Wanderungen bis 20km, Strasse, Pfade, Sand, Felsen, was auch immer im Weg ist.

Meine alten Schuhe sind von Columbia, und die scheinen gut zu passen; in der Vergangenheit war es fast unmoeglich Schuhe zu finden die passen. Was suche ich:

• Schuhe welche unter den Knoecheln enden, keine Stiefel. Dafuer gibt es einen Grund
• nicht wasserfest
• nicht zu schwer, also im Sinne von keinem schweren Leder und Sohle. Aber auch nicht ultralight.
• Die Sohle sollte nicht zu federnd sein. Keine Ahnung ob sowas von Lauf- zu Wanderschuhen ruebergeweht ist
• auch innen am Zehansatz nicht zu weich, weil alte Bruchstelle
• weiter Vorfuss und Zehen
• keine Gewoelbestuetze und genug Breite auch dort.
• auch keine Barfussschuhe. Meine Fuesse sind in jeder Hinsicht einfach nervig und empfindlich. Aber zuviel Polsterung ist halt auch nicht gut.

Nur vom Aussehen her gefallen mir z.B. die Columbia Peakfree Roam oder Konos TRS, aber auch andere kaemen in Frage. Ich kann jedoch nicht alles was irgendwie passen koennte bestellen.

Koennt ihr mir Tipps zu passenden Schuhen geben?

Uff.. impulsiv und autistisch, das ist eine schlechte Kombi, und ich bin jetzt wie gelaemt und weiss nicht was ich tun soll.

Also, ich versuche schon seit Ewigkeiten Antworten zu einem angeborenen Muskelproblem zu bekommen. Zu oft international umgezogen und somit kam ich damit nie weiter. Endlich wurden ein paar Gene untersucht, aber gefunden wurde nur eine Mutation von der 2 Kopien vorhanden sein muessen aber nur eine vorhanden ist. Aber: dieses Gen kontrolliert einen Bereich der Muskeln der schon laenger im Verdacht stand bei mir eine grosse Rolle zu spielen; es gibt Testresultate die in diese Richtung weisen und Symptome scheinen endlich mal zu passen. Es gibt etliche andere Gene die diesen Bereich kontrollieren; keines davon wurde getestet, und alle zusammen sind eher wenig erforscht.

Ich habe also den Hauptautor einer neuen Studie zu diesem Gen (einer von nur 3!) dazu angeschrieben, Resultate und Symptome dazu und gefragt ob dieser mir mitteilen koennte was fuer Laborteste genau dafuer noetig sind, ob jedes Labor das koenne und ob das bei mir ueberhaupt Sinn machen wuerde. Ich bekam eine ganz schnelle Antwort: nur ein Speziallabor in Muenchen kann einen Teil der Teste machen, und diese Forschungsgruppe hat noch einen Rest eines Stoffes der fuer den anderen Teil der Teste in diesem Bereich noetig ist. Einem normalen Unikliniklab fehlt vermutlich die Erfahrung und der Teststoff (wurde vor Ort hergestellt).

Jetzt weiss ich nicht was ich tun soll. In <> von mir geaendert.

Der Forscher hat geschrieben: "Ich kann gerne konsilliarisch die <Probe> mit begutachten und vor allem elektronenmikroskopische Analysen durchführen und schauen, ob die <genannten Dinge> geschädigt sind."

eh.. super! Nur: was jetzt? Eine erneute Probenentnahme ist jedoch geplant - irgendwann. Diese koennte fuer weitere Tests genutzt werden. Theoretisch, denn ich habe keinen direkten Draht zum Spezialisten in meiner Uniklinik; irgendwann wird er, oder eine Sekretaerin mich anrufen mit einem Termin zur Probenentnahme. Emails an die Sekraeterin werden gelesen, immerhin. Ob diese an den Arzt weiterleitet weiss ich nicht. Aber soll ich einfach die Kommunikation mit dem Forscher weiterschicken? Was wird ein Facharzt sagen, wenn man hinter seinem Ruecken sowas macht? und was bedeutet ueberhaupt 'konsiliarisch'? Meine Uniklinik hat vielleicht nicht die funds fuer ausfuehrliche externe Analysen. Und was wenn ich jetzt das letzte bisschen Testsubstanz von einer Person wegnehme die eine viel groessere Chance auf eine Diagnose hat?

Basically: Overthinking! Unsicher wie kommunizieren zwischen Forscher und Facharzt, immer noch unsicher wie deutsches Gesundheitssystem funzt, jemanden anders die Chance auf eine Diagnose nehmen? Argh!

I'm trying to understand the finer details of a human genetic report. I was promised full genome/exome sequencing with results based on search terms. This seems to be the best I can expect here, other than a handful of genes looked at at a time. I guess I got it, though it's not quite what I expected. Germany. Note: I'm not asking whether I have a condition or not. I'm merely asking about the quality of work and chosen methodology here.

Comments:

• upon receiving the result by phone I was told just one heterozygous mutation was found for which I'd need a second allele or another mutation in the same gene. This is also repeated in the clinical part of the letter. I was told nothing else in my whole genome was found that would explain my problems and to come back in 3-5 years.

• I asked whether potential mitochondrial mutations, nDNA or mtDNA were included and I was told it was. Seeing the 'Limitations' section of this report, it looks like mtDNA was not included in this analysis after all, and looking through the list of 66 selected genes, most are congenital myopathies, a few common metabolic myopathies, 8 mitochondrial myopathies, and a few others. About 16 and 10 (thus 26) of these were tested in this university hospital in the same department previously.

• I have the feeling this is far from complete. Given the rarity of my mutation (0,009347%) and no published papers, I wonder whether a heterozygous mutation together with a mutation on a different gene might cause milder, yet lifelong symptoms. I see references to TTN and MYH2, among a few others in relationship with OBSCN, especially where CA^+2 issues and core-like structure in muscle biopsy seem to play a role. None of which were included. No follow-up analysis on related genes was done after this one hit.

Questions: is this a standard methodology, doing a whole genome sequencing and only looking at a few genes? Is search depth and other methods used here normal for such work? Not following up with something that a) fits symptoms and findings and b) might work together with other genes on that part of the body?

The following is a translation, and I hope it makes sense as I used AI for it as this is totally not something I'd be confident translating (sorry!). Things in <> are comments by me

---

Analysis pipeline: megSAP 2025_10

Evaluation software: GSvar 2025_12-59-g062eb7ab

Phenotype

• HPO: HP:0003326 (Myalgia)
• <7 others>

Target region

The target region encompasses at minimum the CCDS ("consensus coding sequence") of the genes listed below ±20 bases of flanking intronic sequence, but may also include additional exons and/or flanking bases.

Name: <deleted as I guess this is confidential>

<list of 66 genes>

filter criteria

• Allele frequency ≤ 0.10%

• Allele frequency (sub-populations) ≤ 1.00%

• Count NGSD ≤ 20

• Impact HIGH, MODERATE, LOW

• Filter columns REMOVE: low_mappability, mosaic, off-target

• Annotated pathogenic KEEP: HGMD, ClinVar (also likely pathogenic)

• Classification NGSD REMOVE: 1, 2

• Classification NGSD KEEP: 3, 4, 5, M

• Variant quality qual≥0 depth≥0 mapq≥0 strand_bias≤-1 allele_balance≤-1 min_occurences≥1 min_af≥0.1 max_af≤1

Total SNVs/InDels found in target region: 646

Number of SNVs/InDels selected for report: 8

Number of CNVs/SVs/REs selected for report: 0

Where present, the following tables capture: pathogenic variants (Class 5) and likely pathogenic variants (Class 4), for which an association with the clinical question can be assumed, as well as variants of uncertain clinical significance (Class 3) for which, considering the literature and the patient's clinical presentation, a contribution to the symptomatology is conceivable and for which further classification of clinical relevance through follow-up investigations may be useful. In some cases — depending on the nature of the genetic change, the family history, and the clinical presentation of the patient — further investigations may result in a change of classification. An (uncommented) list of all detected variants can be requested if needed.

In the presence of specific differential diagnostic indications of a particular disease, further genetic investigations or diagnostic methods may be indicated. For information on the classification of variants, see general supplementary information.

Single nucleotide variants (SNVs) and insertions/deletions (InDels) following clinical interpretation in the context of the clinical question

Variant | Genotype | Gene(s) | Details | Class | Inheritance | gnomAD allele frequency (control cohort) | RNA

chr1:228371738 C>A | het | OBSCN (AR) | OBSCN:ENST00000680850.1:c.23831C>A:p.Ser7944Ter | | n/a | 0.005% | n/a OMIM ID: 608616 Details: GENE=OBSCN_PHENOS=[Rhabdomyolysis, susceptibility to, 1], 620235 (3), Autosomal recessive]

Copy number variants (CNV) and/or structural variants (SV) following clinical interpretation in the context of the clinical question

CNV/SV/RE | Position | Size | Copy number/Genotype | Gene(s) | Class | Inheritance | RNA

None

Coverage statistics target region

Average sequencing depth: 40.28

Average sequencing depth (chrMT): 101.77

<lots of information on the found mutation and classification>

Limitations of the method

• The sensitivity for detection of pathogenic variants in the analysed regions is approximately 95% using the applied methods.

• In homologous regions, the informative value of the analysis is limited.

• The applied methodology is not suitable for specific diagnosis of mosaics. In particular, mosaics with a variant allele fraction below 15% cannot be detected.

• The assessment of variants in the mitochondrial genome is not part of the accredited diagnostics.

So I currently don't live in the Netherlands. I do have a museumkaart that I upgraded from a temporary one. It's kind of yellow/golden on the front. When I received this physical card I was somewhat confused but figured it's just this year's colour. But I visited a few smaller museums this weekend, and the museum staff were confused about my card colour as well. Anyone know what's going on here? Is this the colour for a yearly card that cannot be extended, because no access to iDeal or is something else going on?

Wow, I have to say that this has never happened before, and I do use hostels for city trips regularly. There was some confusion at my hotel with two letter in Antwerp about my room. I wasn't properly checked into it apparently but that was quickly fixed the next morning. This afternoon I returned to my room to find the key not working. Back to reception who insisted I was in the room next door. Ehm.. no? I get a new key for that room, and another one for my old room to take my stuff out. Turns out the old room got turned into a other gender dorm, but all my stuff gone. Bed in new room assigned to me is taken.

Back to reception. Get my bag back, open, stuff thrown in. But fortunately everything still there. Turns out someone cut the lock and threw my bag into the hall where someone else found it and brought it down 😶 Turns out all stuff in my bed is missing though: an original iphone cable, my nighties. And then there's the cut lock. Great. No sign of it, come back tomorrow morning. When I'm on my way again. Reception says no idea and to contact phone service number, phone service says reception needs to sort it. Rush to Hema before they close and buy a new lock and nighties. The cable? Who knows.

Seriously? Please don't tell me I'm the only one this has happened to.

I'm pretty sure I had rhabdo several times as a young child. My remaining parent mentioned bouts of black urine, and I remember the same. No doctor was ever consulted. Born with a mild muscle condition that got worse sometimes around 12-21 or so (could walk uphill as a child, not anymore properly at 16 and 21) and has been stable-ish since. No diagnosis yet decades later due to chaotic life. For past 10 years CK got tested regularly. CK always at near low under all circumstances like yet another ER visit due to overdoing exercise, random test during longer-term barbell training, and self-induced whole-body DOMs from hell to see if it actually does rise. Nope, always around 48-52 (normal: 38-234 nmol/L). What might be the reason for CK to be totally unresponsive? A muscle biopsy found substantial type 2 fiber atrophy. Might this play a role here? I'm exercising 6-7x per week, currently low rep barbell exercises or slow jogging until I hit the wall. Higher reps, even with a cooking spoon in a pot or faster/more strenuous exercising is really the main moment where I notice that something is not right, and that's been like this since my youth. Can bodies build substantial type 1 fibers if type 2 is wrecked? I was quite surprised by the result because I'm fairly muscular and don't experience weakness.

siehe Titel. Reise ist im Juni. nur leider habe ich diese Moeglichkeit nicht im App. Unter More Actions kann ich nur die Rechnung oeffnen oder zu Cancellation gehen, wo jedoch steht, dass keine zur Verfuegung steht. Normalerweise kann ich immer eine neue Verbindung aktiv auswaehlen, auch bei internationalen Fahrten. Hier geht das nicht. Also einfach einen random Zug nach Luxemburg am Reisetag nehmen? Urspruenglich ging diese Fahrt ueber Frankfurt und Koblenz, jetzt kann ich dieselben Fahrzeiten mit anderen Zuegen ueber Mannheim und Trier waehlen. Leider sind das knapp 3 Stunden im RE anstelle ICE, und dann eine kurze Fahrt im RE anstelle einer 2 Stuendigen, aber naja. Alternativ eine Stunde eher und dann das letzte Stueck im Bus von Saarbruecken, wobei ich hier nicht sehen kann ob der Bus im Zugpreis enthalten ist oder nicht. Erwaehnt wird nicht, dass dieses nur ein Ticket fuer eine Teilstrecke ist aber dass ich fuer den Bus einen Sitzplatz reservieren muss. Juhu.

I know that the obsurin gene is huge and controls various things. I wonder what is known so far on pathogenic mutations given that most papers seem to be very new. I had full genome/exome sequencing with search results based on symptoms. A heterocygotic mutation on something autosomal recessive in that gene came up as only thing. One month on I'm still waiting for the report to learn the name of this mutation. The phone call was a 3 minute affair, informing me that this mutation causes burning muscle pain, early fatigue, rhabdo and is related to how muscle cells function and that I need two copies of this mutation. Questions I sent by email after this call remained unanswered. I had just discussed with my neuromuscular specialist a few days before this call that for various reasons I feel my problem is related to how my muscles handle calcium, and here mainly in getting the muscles to relax again after doing anything, really. Based on what I find, parts of this gene seem to be responsible for pushing calcium out of cells and back into the endoplasmatic reticulum. The rest fits as well, even though I've not had rhabdo since childhood for unknown reason. Heck, my CK is always just above lower reference value in whatever situation.

Thus questions: How much is known on this gene and pathogenic mutations on it in general? Is there a possibility to be mildly symptomatic when only having a heterocygotic pathogenic mutation and especially the calcium part, should my mutation be part of that range? Is it possible that this testing was too superficial and there might be other mutations that work hand in hand with OBSCN (damn, love that abbreviation!) that require 'deeper' searching or different analysis to show up?

Way forward is now to get a muscle biopsy to extract mtDNA for further testing, but this will still take a few months to happen, and next appointment in neuromuscular department would be next year. Yeah, things are that slow. Main symptoms: cramps and stiff muscles for hours after doing anything, exercise intolerance, burning and early fatigue but normal strength and endurance building possible, distal muscles worst affected, repeated rhabdo as a child, lots of tests indicating some Mg and Ca issues and exercising on a low level possible if I supplement Mg ahead of it, exercise tests show very early switch to glucose/glycogen and no change despite years of training.

Hi all, I just had an appointment with osteology moved to next month due to their dexa machine breaking down. My gp thinks I should get fully evaluated. Any idea what to expect?

Background: born with a milder muscle condition that has some influence/is influenced by (?) electrolytes. I know that magnesium and phosphate are always low when I just walk 1km to a blood test but normal when I take the car (not for 1km obviously). Mg in 24h urine is always lower than expected despite high supplementation. Calcium so far has not been extensively tested yet. If I supplement Mg I'm able to exercise to some extend. If I don't I can't. Found out over the years that if I supplement vitamin D (often low) or calcium my muscle function is worse than base level and my mobility a lot more limited. If I do something too strenuous then I might end up in ER and magnesium, phosphate, calcium, potassium and bicarbonate end up being low. I suppose at least magnesium and phosphate will be low after every bit of exercise, and here's the problem: exercise -> good mobility -> electrolytes low or not exercise -> electrolytes ok -> mobility limited because muscles work less well. Not sure what happens when I just walk to the supermarket around the corner.

But yeah, referral because I broke 2 bones in 3 years due to nothing really: proximal humerus from stumbling during jogging at granny speed, and metatarsal head from walking on snow. With the first fracture the surgeon doing a second surgery was surprised how quickly the many fractures healed. I guess calcium is ok overall, but the other electrolytes? Not sure. But I am worried.

Main question is whether there are tests that actually test for bone quality, not only density?

1. Laufschuhe bei Amazon bestellt. Ebenfalls Lebensmittel im Glas bestellt.
2. Beides wird zusammen in einem Paket geliefert. Was kann da schon schief gehen.
3. Oeffne Paket am naechsten Tag und finde 200 EUR Laufschuhe vor, mit Lebensmittel, Glas und Pappresten beklebt.
4. Wende mich an Amazon.
5. Amazon bietet an die Schuhe mit Hermes abholen zu lassen. Ich sage: hab keinen Drucker und Karton ist kaputt. Wir einigen uns auf DHL mit Code den ich im Parcelshop ausdrucken lassen kann. Ok, super. Ich lade noch Bilder von der Sauerei hoch.
6. Heute stehen 2 Hermes-Menschen mit Sackkarre vor meiner Wohnung um das kaputte Geraet abzuholen. Ich stelle die Schuhe auf die Sackkarre, die beiden sagen ohne Verpackung und Label geht das nicht. Ja, ist klar.
7. Ich gucke in Account. DHL Label ist noch vorhanden. Ok.
8. Auf einmal Email von Amazon: Geld wurde zurueck ueberwiesen.
9. Ich gucke in Account, Retourlabel ist weg. Ich koenne die Retoure kostenlos bis zum 3. Juni starten.
10. ich gehe ins Bett mit der Frage ob Schroedingers Schuhe morgen mehr Schimmel oder mehr Obstfliegen angezogen haben.

Like seriously slow runner. With a very wide arch area, wide forefoot, and I need a shoe that is hard and stiff underneath the metatarsal head, forefoot rocker.

I love, love, love the feeling of the speedroll, and the Endorphine pro 4 male surprisingly fit and feel so comfy at least for walking. Can't test them outside though. I'm not an average runner: metabolic muscle condition which results in early lowermost leg muscle fatigue when I roll off my feet like you're supposed to. Hence I mostly splash my feet onto the ground if the sole doesn't support me. The shape of this particular plate might help. But due to the same I'm a super slow runner. Like 10km in 80 minutes - if I get that far to start with as I usually hit the wall from 43 minutes at slightly slower pace (shorter runs are slower on average than longer ones). The only other shoes I found that fit are the novablast 5, but they feel a bit too soft and upward bouncy for me. As I can't test them I fear that the endorphine pro 4 only really work from a faster pace. Note, I've been running for 11 years; I'm not a beginner. Just my mitochondria are overall not too happy 😅