Diseases - Block 2

Front 1

dyskeratosis congenita (DKC)

Back 1

Progeria (assoc w. bone marrow failure syndrome)
Accumulation of short telomeres across generations severe the disease phenotype

Front 2

Kartagener’s syndrome

Back 2

aut rec, Mut in axonemal dynein gene.
Lack of dynein arms.
Male sterility due to immotile sperm.
Susceptibility to lung infections due to paralyzed cilia in the respiratory tract (bronchiectasis, sinusitis).
Defects in determination of the left-right axis of the body during early development (situs inversus).

Front 3

Familial hypertrophic cardiomyopathy

Dilated cardiomyopathy

Back 3

ACTIN Affected: heart structure and activity (heart enlargement, small coronary vessels,disturbances in heart rhythm)
Incidence: 2/1000 people, inherited
Cause: mutation in cardiac b myosin heavy chain (in or near motor domain) or other contractile proteins

Front 4

Epidermolysis bullosa simplex

Back 4

KERATIN
Affects: skin, mouth, esophageal lining, eye cornea
Effect: epidermal cells rupture as a consequence of mechanical trauma
Cause: mutation in N- or C-terminal of keratin gene
Clinical symptom: blistering of the skin or other epithelia

Front 5

HGPS Hutchinson-Gilford Progeria Syndrome

Back 5

Upstream cleavage into mature Lamin A is blocked
PROGERIA
die of atherosclerosis at 13

Front 6

Celiac Disease

Back 6

autoimmune disease induced by gluten (a small protein found in wheat, barely and rye), large amounts if indigestible gluten fragments seep into the underlying tissue and incite immune system cells.
LEAKY "tight junctions" of SI

Front 7

Zonulin
blocked by?

Back 7

zona occludens toxin
loosens tight junction

Larazatide blocks zonulin from making gut permeable

Front 8

Pemphigus vulgaris

Back 8

autoimmune skin disease against a cadherin prot, disrupts/impairs desmosomes of skin epithelium.
severe blistering of the skin with leakage of body fluids, loosened epithelium and severe skin lesions that might be fatal, due to secondary infections.
Treated with steroids

Front 9

dentine dysplasia type II

Back 9

DSPP mut (tyr for asp)
failure of translocation of the encoded proteins into the ER--> loss of function of both dentine sialoprotein and dentine phosphoprotein.

Front 10

Congenital Disorders of Glycosylation

Back 10

effects Nervous System
Progeria variant of Ehlers-Danlos
N-glycan assembly/processing dis

Front 11

Perlizaeus-Merzbacher disease

Back 11

CNS-misfolding of PLP membrane prot (proteolipid protein)
misfolded prot is recognized and held in ER instead of transported to cell surface (more ex's of this are antitrypsin, CFTR)

Front 12

Mucolipidosis II

Back 12

I-cell dis (1:350,000) lysosomal storage disease caused by deficient activity of the enzyme N-acetylglucosamine-1-phosphotransferase, which leads to a failure to internalize enzymes into lysosomes.
failure to thrive, behavioral dullness, facial dysmorphia, and ataxia.

Front 13

I-cell disease

Back 13

caused by a deficiency in the enzyme that catalyses the first step in the tagging of lysosomal enzymes with mannose 6-phosphate in the Golgi. The result: a general deficiency in lysosomal enzymes.

Front 14

Myeloma treatment?

Back 14

bortezomib (velcade)

Front 15

Ubiquitin-Proteasome pathway-related clinical disorders =
Mutations causing abnormal folding of a target protein (2)

Back 15

Cystic fibrosis a genetic disease causing severe chronic bronchopulmunary disorders. 25% of the normal CFTR (cystic fibrosis conductance transmembrane regulator) chloride channel molecules reach the cell surface. Mutated CFTR (DF508), is retained in the ER, and degraded via the proteasome after ubiquitin modification.

The Wilson protein a copper transporter, normally localized to the trans-Golgi. Mutated protein is misfolded and retained in the ER, (Wilson disease; disorder of copper metabolism: neuronal degeneration, hepatic cirrohsis)

Front 16

Mutations in the ubiquitin pathway (2)

Back 16

Anglemans syndrome

Parkinson's dis- ARJP

Front 17

Anglemans syndrome

Back 17

rare inherited mental disorder. Truncated ubiquitin ligase (E6-AP) was identified in patients. The target(s) of this ligase has not yet been identified.

Front 18

Parkinson's - ARJP

Back 18

Parkin, an E3 ubiquitin ligase, is associated with autosomal recessive juvenile Parkinsonism. accumulation of unfolded Pael receptor (a substrate of parkin) may cause selective death of dopaminergic neurons in AR-JP.

Front 19

Skeletal muscle wasting

Back 19

occurs in pathological states (fasting, starvation, sepsis and denervation). Activation of the ubiquitin proteasome pathway plays a role in this process

Front 20

Myasthenia Gravis

Back 20

disease of the neuromuscular junction Reduction of ACh receptors by autoantibodies
Treat:Immunosupression, Inhibitors of acetylcholine esterase, Rest

Front 21

Duchenne’s muscular dystrophy DMD

Back 21

progressive disease that begins in early childhood. The individual is unable to walk by the end of the first decade and usually does not survive beyond the third decade (respiratory or cardiac failure).
X-linked recessive (mostly males).
Dystrophin gene defect (protein anchored to the sarcolemma that has actin-binding capabilities).

Front 22

Dystrophic muscle

Back 22

Variations in fiber diameters, internalized nuclei, destruction of myofibrils, sarcomere disorganization, thicker and skewed Z lines, lipid droplets (L) in the sarcoplasm.
Breakdown of muscle fibers and their replacement by fibrous connective tissue (fibrosis).

Front 23

osteopetrosis

Back 23

inactive osteoclasts
DENSE, HEAVY BONES (MARBLE BONES)
BONE RESORPTION IS DEFECTIVE
OSTEOCLASTS LACK RUFFLED BORDER

Front 24

osteoperosis

Back 24

overexpress osteoclasts
reduced activity of osteoblasts

Front 25

Osteoblastoma

Back 25

benign
young adults
upper tibia, upper humerus, lower end of femur
The skeleton is the site of metastases from tumors of:
breast,lung,prostate,kidney,thyroid

Front 26

osteosarcoma

Back 26

Malignant
young adults
upper tibia, upper humerus, lower end of femur
The skeleton is the site of metastases from tumors of:
breast,lung,prostate,kidney,thyroid

Front 27

Mitochondrial fusion and neurodegen dis

Back 27

CMT (charcot-marie-tooth) Mfn2/mitofusion mutation

ADOC (aut dom optic atrophy) OPA1mut

Front 28

Laminopathies

Back 28

IntermFilament - LaminA
Emery Dreifuss Musclular Dystrophy
dilated cardiomyopathy
limb girdle Musclular Dystrophy
familial partial lipodystrophy

Front 29

Cholera

Back 29

ADP-ribosylation
of the a subunit of Gs inhibits gtpase subunit -> constant Gsa-GTP signaling -> constant adenylyl cyclase/cAMP/PKA

inc secretion of Cl/H2O in SI (diarrhea)

Front 30

Pertussis toxin

Back 30

ADP ribosylation on the α subunit of the Gi protein (which normally inhibits adenylyl cyclase) -> inhibits dissociation of Gi-αβγ-GTP -> constant adenylyl cyclase/cAMP/PKA

Resp tract: whooping cough