BS 3 Flashcards by Lo Kola

What is a centromere
What disease is Abs vs centromere

Centromere = central part of the chromosome that holds duplicated sister chromatids together

CREST = anticentromere Abs
Calcinosis
Raynauds
Esophageal dysmotility
Sclerodactyly
Telangiectasia

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Disease for anti-dsDNA Abs

SLE

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Disease for anti-histone Abs
What is a histone

Histone = protein core for spooling DNA
Drug induced SLE

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What is a topoisomerase
Disease for anti-topoisomerase Ab
What abx inhibits

Topoisomerase = DNA gyrase aka unwind DNA for use
Anti-TP Ab = diffuse scleroderma
Quinolone abx inhibit DNA gyrase

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What is the process to make
DNA -> mRNA
mRNA -> protein (and where does this occur)

DNA > mRNA = transcription
mRNA > protein = translation (in ribosomes)

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What proteins are involved in the following steps of transcription:
1 Binds DNA to select genes for transcription
2 Reads DNA to make mRNA
- What abx works at step 2

Transcription factors - bind DNA to tell what parts to code
2 RNA polymerase - reads DNA > mRNA
Abx: rifampin = binds RNA pol = Xs bact RNA synthesis

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Disease for anti-Smith (anti-Sm) Ab
What is a Smith

Anti-Sm = SLE
Smith = snurps
Ribonucleoprotein that cuts out introns, joins exons
- Exon = DNA/RNA that codes for proteins
- Intron = DNA/RNA that does not code for protein

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What is the difference between human vs bacterial ribosomes

Human = 80S = 60 + 40 subunits
Bacteria = 70S = 50 + 30 subunits

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Where do these abx work:
Clindamycin
Macrolides
Linezolid
AminoG
Tetracycline

50S subunit bact ribosome:
Clindamycin
Macrolides
Linezolid

30S subunit bact ribosome:
AminoG
Tetracycline

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Name the disease/mutation/mechanism:
Ragged cafe au lait spots
Precocious puberty
Hypothyroidism
Cushing
Ground glass lesions on XRs

Fibrous dysplasia
Mutation = activation GNAS1
Mechanism = more cAMP

Disorganized fibrotic bone matrix

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What is the disease when fibrous dysplasia is polyostotic

McCune Albright syndrome

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Why is fibrous dysplasia NOT an inherited disorder

Bc is a post zygotic somatic mutation - aka error in the mitosis of the zygote
Mutated genes won’t survive reproduction

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Name the disease/inheritance/mutation/mechanism:
Skin bumps
Smooth cafe au lait
Iris pigmentation
Tibial pseudarthrosis
Scoli

NF1
AD
Mutate tumor suppressor gene
Xs Ras protein = stim cell growth

Hamartomas = Lisch nodules iris, tibial pseudo (AL always looking for a reason for tibial bowing)

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Name 10 common AD diseases (structural proteins!)

1 Achon = FGFR3
3 Pseudoachon = COMP
3 Marfans = fibrillin
4 ED = COL1
5 OI = COL1
6 SED = CO2
7 Kneist = COL2
8 Stickler = COL2
9 MED = COL9, COMP
10 Schmid = COL10

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Name 7 common diseases that are AR (enzyme gene deficits)

1 Diastrophic dysplasia = sulfate transport
2 Hurler = alpha-L-iduronidase
3 Sanfilippo = heparan sulfamidase
4 Morquio = galactose sulfatase
5 Gaucher = cerebrosidase
6 Osteopetrosis = CA
7 Homocystinuria = cystathionine synthase

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Name 5 common XL recessive disease
XL-R disease: who is the carrier, who is affected

Mother = carrier (X*X)
Sons have 50% chance being affected

1 Hunter mucopolysacc = iduronate sulfatase
2 SED tarda = TRAPP
3 Hemophilia (A = F8, B = F9)
4 Duchenne MD
5 Becker MD = DMD gene, Xp21 dystrophin

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XL dominant diseases
- If dad is the carrier, which kids affected
- If mom is the carrier, which kids affected

Dad = XY
All daughters affected XX
No sons (X from mom)

Mom carrier = X*X
50% daughters and sons affected

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What is the general ortho issue for Downs? How does this make sense genetically

COL6 is is on chromosome 21 - overexpressed
Ortho issue = LAXITY
- Hip instab
- Patellar dislocation
- AA instab

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Multiple myeloma
- Genetic cause
- Cell changes
- Lab findings
- Bone findings + mechanisms (2)

Chr 13 deletion = worse prognosis
Proliferate monocolonal B cells = plama cells
Lab = SPEP (M spike), UPEP (Bence Jones proteins)
Bone: lytic lesions
1 Cells release PTHrP = more RANK osteoclast
2 DKK1 inhibits blasts

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Name the disease/mutation/mechanism
Short, fat kid
Hypotonic at birth
MR
Scoli

Prader Willi
Delete paternal ch15
Activates a silent maternal gene

Ewing
- Genetics
- Cells involved
- Presenting sx/population

t(11,22) translocation
- Pat Ewing’s jersey number = 33 (11+22=33)
EWS/FL1 fusion protein
Small blue cells, CD 99 marker (3x33)

KIDS
B sx: pain, fever
Long bone diaphysis

Name the gene translocation:
Synovial sarc
Clear cell sarc
Myxoid liposarc
Myxoid chondrosarc
Rhabdomyosarc

Synovial sarc - t(X, 18)
Clear cell sarc - t(12, 22)
Myxoid liposarc t(12, 16)
Myxoid chondrosarc t(9, 22)
Rhabdomyosarc t(2,13)

What cell is implicated w/ elevated alk phos
3 diseases with elevated alk phos

Alk phos = osteoblasts
Rickets
Osteomalacia
Paget

What is a disease state with LOW alk phos
Inheritance
Gene mutation

Hypophosphatasia
AR
Gene: TNSALP

How does BMP2 work?

Infuse Inflammation -> bone formation Also why see seroma formation

Fibrodysplasia ossificants progressiva: What is it/presentation Pathognomonic finding Inheritance Mutation

Stone man syndrome - see ossification of STRAP + IP muscles Form HO from injury Pathognomonic: 1st ray deformities at birth AD Gain of function BMP receptor = BMP4 over expressed

Which factor controls each: Distal/prox Ulnar/radial Dorsal/ventral

Distal/prox - FGF (via apical ectodermal ridge) Ulnar/radial - SHH (via ZPA) Dorsal/ventral - Wnt / B catenin

Achondroplasia: Inheritance Mutation Which ossification affected Which part of the growth plate affected

AD FGFR3 receptor Endochondral ossification Proliferative zone (where FGF works)

Function FGF23 Disease associated with overactive FGF23 Inheritance/mutation Trt

Trash PO4 - Less renal reabsorption Disease: hypophosphatemic rickets - X dom PHEX mutation = cant breakdown FGF23 = low PO4 Trt = bursoumab = anti-FGF23

Disease associated with low FGF23 activity Cause

Tumoral calcinosis 2/2 chronic renal failure - cant excrete PO4 Occasional genetic disorder that decreases FGF23 CaPO4 deposits throughout the body

3 diseases related to SHH issues

SHH = radio/ulnar Polydactyly (post axial) = too much SSH Mirror hand Fib hemi = too little SHH

Fib hemi: Associated knee finding

Absent ACL

Name the 3 types of tibial bowing and any associated conditions if applicable

AL = Aways Look for NF AM = Absent/Missing bones = fib hemi PM = Probably Mild, +/- calcaneovalgus

What is the classic example of Wnt disorder

Nail patella syndrome Aplastic/hypoplastic patella Iliac horns

Describe intramembranous ossification Is Wnt high or low? How does this affect SOX9/Runx2?

Mensenchymal stem cells direct to osteoblasts No cartilage model Wnt high (osteoblast differentiation) Runx2 high / Sox9 low Ie 1ary bone healing

Cleidocranial dysplasia: Inheritance Mutation Clinical manifestations

AD CBFA/Runx - poor intramemb ossification (flat bones) No clavicles

Describe enchondral ossification Is Wnt high or low? How does this affect SOX9/Runx2?

Stem cells -> chondrocytes = cartilage model, later replaced by bone Ie frx callus, growth plates Wnt low (favors chondrocytes) - increases later when replacing the cartilage matrix w/ bone Sox9 high / Runx2 low

What is the main goal of Wnt

Increase bone!

Osteocytes: How do they communicate What is the main signaling molecule

Communicate via gap jxn w/ connexin Molecule = sclerostin - Blocks Wnt/B catenin = inhibits osteoblasts

What 2 things inhibits sclerostin production? What medicine Xs sclerostin

1 Mechanical loading Sclerostin decreases bone mass Why weight bearing (mechanical loading) = good for bone mass 2 Pulsed PTH Med = romosozumab Approved for osteoporosis

Sclerosteosis: Inheritance Mutation Clinical presentation

AR SOST defect Thick cortices (too much bone) - CN pinching: deaf, blind - No frx bc bones so hard

What does dickkopf protein (DKK1) do

Decrease bone Blocks Wnt/B catenin

Describe the RANK-L/RANK pathway

RANK-L from osteoblasts/cytes Binds RANK Stimulates clast formation RNK is a receptor on clasts

Function of osteoprotegrin

Blocks RANK-L/RANK From osteoblasts How blasts inhibit clasts

What cell does Wnt signaling work on

Mesenchymal stem cells to drive differentiation to osteoblasts

What molecule turns osteoclasts on vs off

On: RANK-L Denosumab is an Ab to RANK-L Off: calcitnoin

2 types of bisphosphonates + mechanism

Nitrogen = block synthase enzyme - Alendronate, risedronate, pamidronate, zoledronate Non-nitrogen = compete with ATP - Tiludronate, etidronate, clodronate

How do osteoclasts break down bone? 4 major cell enzymes

Carbonic anhydrase Cathepsin K TRAP ATPase / Cl- channel