Rapid Review 3 Flashcards
what kind of bonds hold pairs of complementary bases between DNA strands together?
hydrogen bonds
in ONE strand of DNA, what holds the base pairs together sequentially?
3’,5’-phosphodiester bonds
a phosphate group links the 3’ carbon from one sugar to the 5’ carbon of the next sugar
which 2 base pairs have THREE bonds between them when matched up?
and what kind of bond is it?
C & G have 3 hydrogen bonds between them
which 2 base pairs have TWO bonds between them when matched up?
and what kind of bond is it?
A & T have 2 hydrogen bonds between them
which bases are purines?
adenine & guanine
(PURAG)
which bases are pyrimidines?
cytosine
thymine
uracil
(CUTPY)
which bases have 2 rings?
purines - adenine & guanine (PURAG)
(2 pur for this world)
which bases have 1 ring?
pyrimidines
cytosine, thymine, uracil (CUTPY)
(you only need 1 slice of py at a time)
how can you tell adenine & guanine apart?
guanine has a double bonded O (carbonyl group) off the 6C ring
how can you tell cytosine/thymine/uracil apart?
cytosine has one carbonyl (=O) and one NH2 group
thymine has 2 carbonyls (=O) and one methyl arm
uracil has 2 carbonyls (=O)
(the carbonyl =O that they all have is between the Ns in the pyrimidine ring)
what’s ISO 15189:2007
“medical laboratories - particular requirements for quality & competence”
set of standards to promote technical competence and reliability
applies to clin labs, blood banks, HPC labs
true/total turnaround time starts at *** and ends at ***
starts at order time
ends at physician notification time
this measures all pre-, intra-, and post-analytical portions of TAT
which tumor marker is related to the Lewis blood antigen?
CA 19-9
Le- patients (black pts) don’t make Lewis and also don’t make CA 19-9
what does a western blot look at?
proteins
(they eat beef in the west)
what does a Northern blot look at?
RNA
noRth = Rna
what does a Southern blot look at?
DNA
(because they share a lot of DNA in the south)
what is the most common quantitative method to measure sweat chloride in suspected CF patients?
coulometric titration procedure
(Cl ions in sample react with silver ions from a silver electrode –> AgCl)
what do you need to know about the Jaffe reaction
measure rxn rate between 20-60 seconds (this is when Creatinine specifically reacts with picric acid)
Cr + picric acid in alkaline solution > orange-red complex > measure @ 520 nm
what should you use instead of GFR if your patient is 3 months old or younger?
cystatin C
(better indicator of renal fxn)
toxicity with WHAT presents like a pheochromocytoma?
mercury
think of the mad hatter: hypertension, tachycardia, pruritis, desquamating rash on palms, poor muscle tone
what’s the mutation in Wilson disease
ATP7B mut
autosomal recessive
ANA testing
what does Sjogren look like?
nucleolar pattern
few large dots
ANA testing
what does lupus look like?
diagnostic: rim/outline/peripheral
but can also be homogeneous
these are both c/w dsDNA
ANA testing
what does CREST look like?
centromere
(crest centromere)
what tumor marker should you use for pancreatic carcinoma?
CA 19-9
(but not in Lewis negative patients)
you can also use CEA
what tumor marker should you use for GI or pancreatic cancer?
CEA
what tumor marker should you use for ovarian cancer?
CA-125
(HE4 also but not standard)
what tumor marker should you use for monitoring lung cancer?
CEA
what tumor marker should you use for monitoring breast cancer?
CA 15.3
what’s the bad part about heterophile antibodies?
they bind to the capture AND the labeled antibodies, so you get a falsely elevated result
ewing sarcoma/PNET mutation
t(11;22) EWSR1-FLI1
Peutz-Jeghers
mode of inheritance
mutation
clinical
autosomal DOMINANT
SKT11 mut (19p13.3)
hamartomatous colon polyps, panc/breast Ca, ovarian SCTAT (sex cord tumor with annular tubules)
WAGR syndrome
mode of inheritance
mutation
clinical
sporadic?
WT1 del11p13.3
WAGR = Wilms tumor, Aniridia, GU abn, and mental Retardation
(auto dom PAX6 del11p = just aniridia)
Beckwith-Wiedemann
mode of inheritance
mutation
clinical
auto DOMINANT
mut/del of imprinted genes in 11p15.5 (CDKN1C, H19, IGF2, KCNQ1OT1)
loss of methylation @ imprinting center 2 on maternal chromosome is MC, followed by paternal uniparental disomy
macroglossia, exomphalos, gigantism, predisposition to Wilms tumor, hepatoblastoma
Li-Fraumeni
mode of inheritance
mutation
clinical
auto DOMINANT
TP53 mutation (chromosome 17 [17 x 3 = 51 lmao])
sarcomas, breast cancer, glioblastoma, adrenocortical adenoma/carcinoma, leukemia/lymphoma
tumor suppressor genes - name 7
Rb
p53
VHL
APC
BRCA2
NF1
PTCH
proto-oncogenes - name 6 (and an extra via fusion)
receptor tyrosine kinases (EGFR, PDGFR, VEGFR, Her2/neu)
RAS
WNT
MYC
ERK
TRK
extra via fusion: Philadelphia chromosome t(9;22) BCR-ABL1
hereditary diffuse gastric cancer
mode of inheritance
mutation
clinical
auto DOMINANT
CDH1 mut (usu truncating) (this is e-cadherin, duh) (chrom 16)
diffuse signet ring cell Ca of stomach, lobular breast Ca
Legius syndrome
mode of inheritance
mutation
clinical
auto DOMINANT
SPRED1 mut (chrom 15)
cafe au lait spots & macrocephaly (“NF1-lite”)
what are the 3 founder mutations in BRCA1/2 in Ashkenazi patients?
BRCA1 185delAG
BRCA1 5382insC
BRCA2 6174delT
(all 4 bases, numbers 1-8, couldn’t be worse)
order of appearance of Hep B labs
- HB S Ag
- HBe Ag
- total anti-Hb core
- anti-HbE
- anti-HbS
which blood group is H pylori associated with?
H & Lewis B Ag
which blood group is parvo associated with?
P ag
which blood group is plasmodium vivax associated with?
duffy
what are the 5 clinically significant/abnormal urine crystals?
ACABS
- amino acids (tyr, leu, cyst)
- cholesterol
- ampicillin
- bilirubin
- sulfonamides
they’re ALL ACIDIC
what urine crystal is this?
what does it mean?
amorphous urates - pink/orange, acidic urine
it means the sample sat around
what urine crystal is this?
what is it due to?
uric acid
due to gout
***birefringent under polarized light (bc gout)***
what urine crystal is this (and which form)?
what does it mean?
calcium oxalate dihydrate (octahedral [stud])
can be normal, can be ethylene glycol
what urine crystal is this (and which form)?
what does it mean?
calcium oxalate monohydrate (dumbbell)
can be normal, can be ethylene glycol
what urine crystal is this?
what does it mean?
bilirubin (can be other shapes, always yellow-brown)
liver disease
always abnormal
what urine crystal is this?
what does it mean?
tyrosine (sheaves of wheat)
sometimes seen in severe liver disease
(you see this more often than leucine bc it is less soluble in acidic urine)
what urine crystal is this?
what does it mean?
leucine (refractile yellow-brown spheres w/ lamellations)
can be seen in severe liver dz
easily mistaken for fat globules, however leucine will not stain with fat stains or appear as maltese cross under polarization
what urine crystal is this?
what does it mean?
cysteine (clear hexagon)
congenital cystinosis, cystinuria, homocystinuria (kidney damage)
can be confused with uric acid crystals - use sodium cyanide test - cysteine will be positive/purple bc cystine + cyanide > cysteine > binds to nitroprusside
what urine crystal is this?
what does it mean?
ampicillin (long thin needles)
RARE - seen with megadoses of ampicillin
what urine crystal is this?
what does it mean?
acyclovir
they’re birefringent, too
not sure what they mean other than watch out for renal injury?
what urine crystal is this?
what does it mean?
cholesterol
RARE! think nephrotic syndrome
seen with positive protein & fat droplets, fatty casts, oval fat bodies
what urine crystal is this?
what does it mean?
sulfonamide (birefringent)
RARE nowadays
what urine crystal is this?
what does it mean?
amorphous phosphates - colorless, normal!
enhanced with refrigeration
what urine crystal is this?
what does it mean?
triple phosphate/STRUVITE
coffin lids
can be normal, a/w UTIs & stones
what urine crystal is this?
what does it mean?
struvite/triple phosphate
fern leaf/feather form
can be normal or a/w UTI/stones
what urine crystal is this?
what does it mean?
calcium phosphate (aka stellar phosphate)
what urine crystal is this?
what does it mean?
ammonium biurate (thorny apple)
usually seen in OLDER specimens, only significant if in ~fresh samples
what urine crystal is this?
what does it mean?
calcium carbonate
very very smol
less fibrillar than calcium oxalate
how does collagen function in thrombus formation?
- binds to GpVI & GpIa-IIa receptors on plt surface
- GPVI: plt signaling & TXA2 generation
- GpIa-IIa: plt adhesion
- granule release & TXA2 generation
- sustained GPIIb-IIIa activation
how does ristocetin cause platelet agglutination?
why not aggregation?
GpIb-V-IX complex & vWF
aggregation requires fibrinogen binding to GpIIb-IIIa
what is the key for plt aggregation in aggregometry?
aggregation requires fibrinogen binding to GpIIb-IIIa
how does ADP function in plt aggregometry?
binds to ADP receptor on plt > shape change > Ca release > primary wave
dense granules release ADP > secondary wave
what are the ADP receptors on plts?
GPCRs P2Y1 and P2Y12
target for clopidogrel
P2Y12 (ADP receptor on Plt)
what does adrenaline bind to in aggregometry?
alpha2-adrenergic receptor on plt surface
then mediates the same stuff as ADP (Ca release, primary wave with dense granules, secondary wave)
how does thrombin work in aggregometry?
activates plts
activates protease-activated receptors PAR1 and PAR4
what is this one
everything normal BUT high-dose ristocetin
so it’s either Bernard-Soulier or vWD 2A
because Bernard-Soulier and vWD 2A can have the same aggregometry, what can you do to differentiate them?
add plasma with vWF > this corrects the response to ristocetin in vWD 2A
what is this one?
only responded to ristocetin
Glanzmann thrombasthenia or afibrinogenemia
(bc plt agglutination with ristocetin does NOT NEED fibrinogen! so the fact that it only responded to risto means that it’s missing fibrinogen or it didn’t bind fibrinogen to GPIIb-IIIa)
what is this one?
storage pool disorder or defective nucleotide release
reversible 1st wave aggregation in ADP, adrenaline, & collagen
partial agglutination with ristocetin
what will aggregometry with aspirin look like?
NO RESPONSE TO ARACHIDONIC ACID
primary only with ADP
decreased or absent response with collagen
what will the aggregometry for clopidogrel look like?
NO RESPONSE TO ADP
What will the aggregometry for VWD 2B look like?
agglutination with low-dose risto
how will TEG look with anticoagulants/hemophilia/factor deficiencies?
decreased max amplitude
decreased angle
LONG R & K
so stretch the whole thing out
(compare top/normal to middle/anticoag; ignore bottom)
how will TEG for DIC look?
stage 1: hypercoagulable with secondary fibrinolysis (picture)
stage 2: hypocoagulable
how will TEG look with plt blockers?
normal R, normal angle (this is the main diff from anticoagulants/factor deficiencies)
prolonged K
decreased max amplitude
what does TEG for fibrinolysis look like?
R is nomral
MA will decrease quickly
do the TEG patterns as glasses
normal = brandy snifter
factor deficiency = wine glass
fibrinogen deficiency = champagne flute
thrombocytopenia/plt issue = test tube
fibrinolysis = martini glass, backward
what should you give a patient with a factor deficiency?
factor concentrate
or
FFP
what should you give for fibrinogen deficiency?
cryo
what should you give a patient with thrombocytopenia/thrombocytopathy (think about TEG)
platelets
what should you give a patient with fibrinolysis?
TXA
what factors are in the intrinsic pathway?
12, 11, 9, 8
what factors are in the extrinsic pathway?
7
what factors are in the common pathway?
10, 5
2 (pro/thrombin)
protein C > APC
protein S
thrombomodulin
1 (fibrinogen/fibrin)
13 (last)
what part of the clotting cascade does PT evaluate?
extrinsic
factor 7
what part of the clotting cascade does PTT evaluate?
intrinsic
12, 11, 9, 8
what drug inhibits the intrinsic pathway most?
heparin
what drug inhibits the extrinsic pathway most?
warfarin
(& I imagine common, bc of 2 and 10)
what is this
sporothrix schenckii
what is this
sporothrix schenckii
storage requirements
whole blood
1-6C
CPD/CP2D/ACD: 21 days
CPDA-1: 35 days
storage requirements
RBCs
not frozen or irradiated
1-6C
CPD/CD2D/ACD: 21 days
CPDA-1: 35 days
CPD+AS1/3/5: 42 days
what’s the biggest storage difference between whole blood and RBCs?
you can use additive solution (AS1/3/5) with RBCs but not whole blood
AS extends the shelf life to 42 days
storage requirements
frozen RBCs
-65C or less
10 years
24 hours after thaw
storage requirements
irradiated RBCs
1-6C
28 days
(irradi8ed)
storage requirements
platelets
random
20-24C with agitation, 5 days
20-24C without agitation, 24 hours
after pooling: only 4 hours!
storage requirements
platelets
apheresis
20-24C with agitation, 5 days
20-24C without agitation, 24 hours
storage requirements
FFP
-18C or less
1 year
OR
-65C
7 years
storage requirements
cryo
-18C or less
1 year
what temp do you MAKE cryo at?
1-6C
storage requirements
granulocytes
22-24C
24h! that’s it!
what should you collect for postmortem evaluation of DKA?
vitreous
how much iron is in one unit of RBCs?
200 mg
name the defective enzyme
Tay-Sachs
hexosaminidase A
name the defective enzyme
Fabry disease
alpha-galactosidase A
name the defective enzyme
Gaucher disease
glucocerebrosidase
(beta-glucosidase)
name the defective enzyme
metachromatic lekuodystrophy
arylsulfatase A
name the defective enzyme
Krabbe
galactocerebrosidase
name the defective enzyme
Niemann-Pick
sphingomyelinase
which disorder has this cell?
Gaucher
which disorder has these cells?
Niemann Pick
foam cells
Fragile X
gene/chromosome
repeat
FMR1 on X
CGG repeat (fraGile in C-G)
Friedrich’s ataxia
gene/chromosome
repeat
FXN/FA on chromosome 9 (friedrich has 9 letters)
GAA (the outlier)
Huntington disease
gene/chromosome
repeat
HTT on chromosome 4
CAG repeat (hunter’s CAGe in C-G)
myotonic dystrophy type 1
gene/chromosome
repeat
DMPK on chromosome 19
CTG
which trinucleotide repeats are loss of function?
fragile X (CGG)
Friedrich ataxia (GAA)
which trinucleotide repeats are gain of function?
Huntingon (CAG)
Spinocerebellar ataxia (CTG)
myotonic dystrophy type 1 (CTG)
which trinucleotide repeat occurs in coding regions?
Huntington (CAG)
which trinucleotide repeat happens in the 5’ UTR?
fragile X (CGG)
spinocerebellar ataxia 8 (CTG)
which trinucleotide repeat happens in the 3’ UTR?
myotonic dystrophy type I (CTG)
which trinucleotide repeat happens in an intron?
Friedrich ataxia (intron #1 of FA/FXN gene)
inheritance of Huntington disease
autosomal DOMINANT
inheritance of fragile X
X-linked DOMINANT
what are these and what disease do you see them in?
zebra bodies
Niemann Pick
accumulated substrate & inheritance
Fabry
ceramide trihexoside (globotriaosylceramide)
x-linked recessive
[deficiency in alpha galactosidase A]
accumulated substrate & inheritance
Gaucher
glucocerebrosidase
auto recessive
[glucocerebrosidase def]
accumulated substrate & inheritance
Niemann Pick
sphingomyelin
auto recessive
[sphingomyelinase def]
accumulated substrate & inheritance
Tay-Sachs
GM2 ganglioside
auto recessive
[hexosaminidase A def]
accumulated substrate & inheritance
Krabbe
galactocerebroside/psychosine
auto recessive
[beta-galactocerebrosidase def]
accumulated substrate & inheritance
metachromatic leukodystrophy
cerebroside sulfate
auto recessive
[arylsulfatase A def]
deficient enzyme in Hurler’s
alpha-L-iduronidase
accumulated substrate & inheritance
Hurler’s
heparan sulfate + dermatan sulfate
auto recessive
[alpha-L-iduronidase def]
accumulated substrate & inheritance
hunter’s syndrome
heparan sulfate + dermatan sulfate
x-linked recessive
[iduronate sulfatase def]
deficiency in hunter’s syndrome
iduronate sulfatase
clinical
Fabry
early: peripheral neuropathy, angiokeratomas, hypohidrosis
late: cardiovascular & progressive renal dz
clinical
Gaucher
HSM
pancytopenia
osteoporosis + avascular necrosis of femur + bone crises
Gaucher cells
clinical
Niemann-Pick
HSM
neurodegeneration
cherry-red spot on macula
foam cells
clinical
Tay-Sachs
neurodegeneneration
cherry red spot on macula
lysosomes with onion skin
NO HSM
clinical
Krabbe
peripheral neuropathy + destruction of oligos + optic atrophy
globoid cells
clinical
metachromatic leukodystrophy
central & peripheral demyelination
ataxia + dementia
what are these & what disease do you see them in?
lysosomes with onion skin
Tay-Sachs
what are these & what disease do you see them in?
globoid cells
Krabbe
which lipoprotein has the most cholesterol?
LDL
which lipoprotein has the most trigylcerides
VLDL
(except nascent VLDL is mostly triglycerides, like chylomicrons)
which lipoprotein has the most protein?
HDL
(the main protein is ApoA-1)
what is the main component of chylomicrons?
triglycerides
which lipoproteins are unaffected by fasting?
which one is absent in fasting?
unaffected: HDL and total cholesterol
chylomicrons are absent in fasting states
what’s the apoprotein in LDL?
ApoB
what’s the apoprotein in HDL?
ApoA-1
what’s the friedelwald formula
LDL = total - HDL - VLDL
VLDL = trigly/5
mechanism for statins
HMG-CoAR inhibitors > decrease cholesterol synthesis > increase upregulation of LDL receptor synthesis
hyperlipidemia type 1
what is high
what’s the problem
high chylomicrons & triglycerides
LPL deficiency
hyperlipidemia type 2a
what is high
what’s the problem
high LDL
problem with LDL receptors (mutation on either LDLR, PCSK9, or APOB)
hyperlipidemia type 2b
what is high
what’s the problem
high LDL & triglycerides (familial combined hyperlipidemia)
issue with LDL receptors (mutations in LDLR, PCSK9, or APOB)
how do PCSK9 mutations work?
they change the # of LDL receptors on the cell surface
GoF: fewer receptors, higher LDL in plasma
LoF: more receptors, lower LDL in plasma
hyperlipidemia type 3
what is high
what’s the problem
“broad beta-VLDL” (familial dysbetalipoproteinemia)
E2 homo: higher trigly
E4 homo: higher cholesterol (Alzheimer)
hyperlipidemia type 4
what is high
what’s the problem
high VLDL (familial hypertriglyceridemia) (bc VLDLs are mostly trigly)
LPL deficiency
not Mendelian
hyperlipidemia type 5
what is high
what’s the problem
mixed hyperlipidemia so high chylo & high VLDL/trigly
USF1/APOA5 mut
familial defective apolipoprotein B-100
what is high
what’s the problem
high LDL
APOB gene mutation > decreased LDLR affinity > more LDL in circulation
which hyperlipidemia does NOT have an increased risk of coronary athero?
type 1 > hyperchylomicronemia
primary hypoalphalipoproteinemia
what is high
what’s the problem
defective APOA1 gene > HDL catabolism > low HDL
clinical presentation of Tangier disease/familial alphalipoprotein deficiency
orange hyperplastic tonsils, peripheral neuropathy, splenomegaly
genetics of Tangier/familial alpha-lipoprotein deficiency
auto recessive
defective ABCA1 gene > cholesterol can’t get out of cells > low HDL
what is fish-eye disease?
partial LCAT deficiency > affects alpha-LCAT > cholesterol can’t attach to HDL > low HDL
auto recessive
what is complete LCAT deficiency?
impaired alpha & beta-LCAT > affects HDL, LDL, and VLDL
cloudy corneas, kidney issues, hemolytic anemia, HSM, LAD
what is CETP deficiency?
atuo recessive
impaired cholesterol ester transfer > they stay on HDL > apoA1 is increased, HDL is increased
what are the mismatch repair subtypes?
MSI-H with any BRAF = best
MSI-H BRAF-wt KRAS-wt = v good
MSS BRAF-mut = bad
when can you NOT use anti-EGFR therapy in MMR colon cancer?
KRAS mut = resistance
BRAF & NRAS mut = “reduced sensitivity”
if your MMR IHC is positive (like you have loss), how do you differentiate sporadic vs Lynch?
MLH1 promoter methylation = sporadic
no methylation = germline mutation = Lynch
what is the BRAF status of Lynch colon cancer?
wild type
what is the most common pathogenesis of sporadic colon cancer?
chromosomal instability
APC inactivation > activating KRAS mut OR BRAF mut (not both) > activating NRAS &/or PIK3CA mut
what codon positions prevent EGFR sensitivity in sporadic colon cancer with KRAS mutations?
codon 12, 13, 61
how does the sessile serrated pathway work in colon cancer?
CpG island hypermethylation in tumor suppressor genes + BRAF V600E mut
what is the order of commonality of MMR gene mutations in Lynch?
MSH2 50%
MLH1 30-40%
MSH6 7-10%
PMS2 <5%
T/F: Lynch syndrome patients can have BRAF-mut colon cancer
NO THEY CANNOT so FALSE
Peutz-Jeghers
inheritance & gene
AUTO DOMINANT
STK11 mut (11 Spots on Their Kissers)
mutation in
synovial sarcoma
t(X;18)
SS18 (on 18) + SSX1, SSX2, or SSX4 (all on X)
mutation in
alveolar rhabdomyosarcoma
t(2;13) FOXO1(13)/PAX3(2)
or
t(1;13) FOXO1/PAX7
mutation in
myxoid liposarcoma
t(12;16)
FUS(16)-DDIT3(12)
mutation in
PNET/Ewing sarcoma
t(11;22)
EWS (22)/FLI1 (11)
mutation in
hereditary diffuse gastric cancer
truncating mut in CDH1
mutation in
prostate adenocarcinoma
UBE2L3-KRAS
(KRAS fusions)
what is the ALK alteration you can get in lung cancer?
inv(2) EML4-ALK
mutation in
ALCL
t(2;5) NPM1-ALK
IHC will be + in nucleus & cytoplasm (variants will be cytoplasm only)
mutation in
inflammatory myofibroblastic tumor
ALK translocations
ALK is on 2
mutation in
Glanzmann thrombasthenia
ITGA2B & ITGB3
mutation in
Sturge-Weber
GNAQ p.R183Q
on chromosome 9
mutation in
VHL
the gene is also VHL (tumor suppressor)
on chromosome 3
mutation in
alpha 1 antitrypsin
SERPINA1 p.E342K
chromosome 14
mutation in
heparin cofactor II deficiency
SERPIND1
chromosome 22
mutation in
familial adenomatous polyposis
APC p.I1307K
(APC is a tumor suppressor)
IHC: upreg b-cat, inc cmyc & cyclinD1
mutation in
MUTYH-associated polyposis
MUTYH
defective DNA damage repair
mutation in
xeroderma pigmentosum
XPC, ERCC2
defective DNA damage repair/nucleotide excision repair
(less common POLH which is not nucleotide excision repair related)
mutation in
hemochromatosis
HFE p.C282Y
chromosome 6
mutation in
sporadic & familial neuroblastoma
ALK p.R1275Q
ALK is on chromosome 2
mutation in
factor V Leiden
FVL mutation @ APC cleavage site (1691G>A)
(chromosome 1)
much worse with prothrombin G20210A mutation
mutation in
familial hypocalciuric hypercalcemia
CASR gene on 3q
BRCA1 specific mutations in Ashkenazi Jewish pts
185delAG
5382insC
mutation in
GIST
GoF in KIT
(chrom 4)
mutation in
piebaldism
LoF in KIT
(chrom 4)
mutation in
NF1
von Recklinghausen so chromosome 17
NF1 = neurofibromin = RAS inhibitor
mut = RAS activation > neurofibromas
mutation in
NF2
NF2 so chromosome 22
merlin/schwannomin mut = LoF in contact inhibition = uncontrolled prolif
mutation in
Legius syndrome
SPRED1
(chrom 15)
(NF1 lite)
mutation in
Costello syndrome
HRAS
(chrom 11)
auto DOMINANT
[faciocutaneoskeletal syndrome: cutis laxa, papillomata, palmoplantar hyperkeratosis, cardiomegally, macrocephaly/acromegalic]
what genes are the cardiofaceocutaneous and Noonan syndromes associated with?
KRAS
NRAS
HRAS (Costello)
BRAF
MEK2
(oncogenes!)
mutation in
Smith-Magenis syndrome
del17p11.2
either del or mut RAI1
mutation in
cockayne syndrome
auo recessive
ERCC6 or ERCC8
chromosome breakage syndrome
mutation in
ataxia telangiectasia
auto recessive ATM mut
inc freq of tri-radial, ring, translocated chromosomes induced by ionizing radiation or bleomycin
(chromosome breakage syndrome)
mutation in
Fanconi anemia
auto recessive FANCA, FANCC, FANCG mut
chrom breakage syndrome a/w treatment with mitomycin c/d
weird THUMBS, markedly inc risk for AML & MDS > pancytopenia > marrow failure
mutation in
Diamond-Blackfan anemia
mut in RPS19 (ribosomal subunit protein)
pure red cell aplasia > MDS & AML
cleft palate, extra fingies
(diamond ring on your finger, black BM bc no RBCs)
what’s the name of the inherited bone marrow failure syndrome that has issues with telomere maintenance?
dyskeratosis congenita
TERT, TERC, DKC1, or TINF2 genes
which bone marrow failure syndrome has pancreatic insufficiency?
Schwachman-Diamond syndrome
mutation in
Schwachman-Diamond syndrome
mutation in the Shwachman-Bodian-Diamond syndrome (SBDS) gene on chromosome 7
which inherited disorder has issues with nucleotide excision repair?
xeroderma pigmentosum
nucleotide excision repair removes thymine dimers, photoproducts, chemical adducts, and cross-links
mode of inheritance for xeroderma pigmentosum
auto recessive
9 genees in nucleotide excision repair are involved and I am not going to remember them
what’s the most common genetic disorder in Puerto Rico?
Hermansky-Pudlak
mutation/mode of inheritance in
Hermansky-Pudlak
auto recessive
many genes, most are HPS#
what should you look for on flow in Hermansky-Pudlak?
decreased/absent CD63
mutation in
Kallman syndrome
KAL1 gene (delXp22.3)
hypogonadism & anosmia (GnRH neurons stay in olfactory bulbs & never migrate to hypothalamus)
[this is the same delXp22.3 as ichthyosis]
mutation in
ichthyosis
delXp22.32
steroid sulfatase gene (STS)
[this is the same delXp22.3 as Kallman]
mutation in
retinoblastoma
del13q14.1-q14.2
RB1 is on 13q
mutation in
Beckwith-Wiedemann
del/mut of imprinted genes within 11p15.5
***MC: loss of methylation at imprinting center 2 (IC2) on maternal chromosome
[Russell-Silver has issues with the same locus and also imprinting]
mutation in
DiGeorge syndrome
del22q11.2
DGS1 or DGS2
1.5-3.0 megabase hemizygous deletion
physical manifestations: haploinsufficiency of TBX1
mutation in
cat eye syndrome
supernumerary marker chromosome from chrom 22
what is the most common inherited disorder of the peripheral nervous system?
charcot-marie-tooth
what is the most common genetic mutation in charcot-marie-tooth?
dup/mut of PMP22 on 17p12
type 1A - auto DOMINANT
mutation in
Williams syndrome
deletion on chrom 7
ELN
mutation in
WAGR
also what does that stand for?
WT1 or PAX6 del11p13.3
Wilms - Aniridia - GU malformations - mental Retardation
mutation in
Wolf-Hirschorn
4p-
mutation in
cri-du-chat
del5p15 (5p-)
mutation in
Miller-Dieker/lissencephaly
del17p13.3
LIS1
