NBME 20 Heterozygous mutation in the ankyrin gene (NBME Answers)

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nbme20/Block 3/Question#11 (60.2 difficulty score)
A 3-year-old boy is brought to the physician ...
Heterozygous mutation in the ankyrin gene🔍,📺
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+12
submitted by nala_ula(113),

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heT ghtiosoyl is fo shyeecstorp mllas( scerilpah llsce /ow tacrlne o.)ralpl arriedyHte ihsoectsspyor si eud to cdefte ni tpensiro ticeargnnti whit CBR nmeeambr keesnotl nda sapmla abenmmre yna,rin(k bnda ,3 tepnroi .24, )precnti.s tMyslo otsaalmuo mnoitadn ierhtincnea s(o yreotguohsez untaitom nices oyu loyn deen eno mttaun llalee to egt het isas)dee.

wuagbe To add to this: homozygous HS presents with hemolysis even in absence of stressors. this patient is only presenting with pale skin, and there are no schistocytes on the peripheral smear, so it's a heterozygous ankyrin mutation. +8

pg32 I wanted to pick hereditary spherocytosis but the mean corpuscular concentration was normal and I thought it was supposed to be elevated? Also, why are there so many RBCs that are way bigger than the spherocytes? +6

nephroguy I'm assuming that the MCC is normal because the patient is heterozygous for HS. Not sure if this is correct, but that was my thought process +1

draykid Are there any papers that explain the difference in expression of homozygous vs heterozygous HS? +20

waterloo I don't know if that matters as much, like the phenotype difference of homozygous or heterozygous for this question. Since you only need one allele to show this, play odds. Is he more likely to have AA or Aa. That was my thought process. Also if you see spherocytes you'd be going for ankyrin right, not B-globin bc that should be target cells - regardless of MCHC. +1

alimd as I remember AD are always heterzygous. Because homozygous are always lethal. +4

+3
submitted by xw1984(5),

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I otg hist Q nwogr. I aws nwnogidre wyh tihs ntiptea as“h no rsloenap or miafly tor.i”ysh rtedeayiHr srsotoshicype losduh eb a DA sa,isdee ,so ayegerlln epsig,nak shit idz ouhsld eb eesn ni ceha aeg,tornnei tg?irh

step1soon I was thinking the same! +

wuagbe Several genetics questions on NBME20 appear to be trying to throw us off by changing the descriptions of inheritance, leaving us to assume incomplete penetrance, smh. +

+3
submitted by dr_jan_itor(71),

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nCa oneyan esanwr wyh stih eno tc'an be .F eBta tehamasail j?oram I was igntkinh seaebcu of shi emnaia dan het "oaeupner cnetes"d hcwih lueisdcn the meartineadin p.eseouarn nlsUse EMNB wsrrtei kniht tath raeuneop oyln easmn eth oesn twih eaxtr ehiwt eelopp llo

dickass European implies northern european (they even specified the patient was a person of pallor), mediterranean descent is usually implied by country of origin or by straight-out writing 'mediterranean'. +

poisonivy The MCV is normal, thalassemias are microcytic anemias, that hint helps to rule out the thalassemias. However, I got it wrong, not sure why it cannot be a homozygous mutation in the ankyrin gene +2

adong @poisonivy, other commenter pointed out it's autosomal dominant so best answer would be heterozygous +

+1
submitted by sciguy(1),

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SH is maotaolus om,nanidt utb estxiihb limteoecnp nret.ecnepa So eh had on dceror of loaesnpr ylmi,fa btu illts yellik gsuorzhty.ee

kdii(p)iWea heT icialcln ieytersv fo HS evsria rofm fromtpseemy- erricar ot evesre hmeslsiyo useebac eth ddoiserr tsxhiieb etplonecmi cannteeerp ni tsi sr.snoexipe

ibestalkinyo This is what threw me off; I figured with 2 unaffected parents, it's more likely he had an autosomal recessive mutation. +1

+0
submitted by strugglebus(165),

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toAu dmo aieessd rae usluyla ohoseretuzyg r(o os ythe nawt us ot sa)usem

xxabi How do you know is autosomal dominant? +3

scpomp Hereditary spherocytosis +

fshowon Isnt the mean corpuscular hemoglobin concentration increased in spherocytosis? Thats what through me off. +5

charcot_bouchard yes, would be inc in prev NBME. But this is batshit nbme 20. U have to identify spherocytes without central pallor in PBF +4

charcot_bouchard yes, would be inc in prev NBME. But this is batshit nbme 20. U have to identify spherocytes without central pallor in PBF +

+0
submitted by victor_abdullatif(2),

I think the key to this question is to use elimination for facts that we know for sure. The first is that it's a normocytic anemia, so all thalassemias are rule out since thal = microcytic.

That leaves A and D. Since the MCHC is normal (which is not what we would expect for hereditary spherocytosis) and the patient's symptoms are severe, they must have a "milder" version of the disease (e.g. achondroplasia is also autosomal dominant and is lethal if you get the homozygous form).

Obviously some big leaps in reasoning here but that's one path to the right answer

victor_abdullatif edit #1: made a typo. meant to say "the patient's symptoms are NOT severe" sorry about that! +