Exam 1 Clinical CorrelationsUTF8 Flashcards
Wiskott-Aldrich Syndrome (WAS)
mutated WASP protein controlling actin assembly, skin lesions, immune system defects
Hypertrophic Cardiomyopathy
cardiac alpha-actin, problems with contraction and force transmission, leading cause of sudden cardiac death in young adults
Amyotrophic Lateral Sclerosis (ALS)
actin protein profilin-1 mutation causes familial form; progressive dysfunction and death of motor neurons; leads to atophy of muscle cells
Extra (I think): also SOD1 mutation affecting fast axonal transport via defect in kinesin but not dynein; 90% sporadic, 10% familial; dying-back neuropathy
Alzheimer’s Disease (AD)
microtubule-associated protein Tau involved in trafficking of materials and formation of neurofibrillary tangles, accumulation of IF neurofilaments
Extra: oligomeric amyloid-beta affects kinesin and dynein; modified or unstacked Golgi
Frontotemporal Dementia and Parkinsonism (FTDP)
mutation in FTDP-17, presents as a tauopathy in cortical neurons
Hereditary Spastic Paraplegia (HSP)
most common is spastin mutation
Extra: presents as dying-back neuropathy in upper motor neurons, can also be heterozygous mutation in neuron-specific kinesin 1A (homozygous is embryonic lethal)
Lissencephaly
Most common mutation is Lis1, a dynein-associated protein that anchors dynein to specific locations in cell; defect in neuronal migration, perturbs layering of cortex, which is smooth instead of normal gyri (also mutations in doublecortin and tubulin 1a)
Congenital Fibrosis of Extraocular Muscles Type 3 (CFEM3)
beta 3 tubulin mutation affecting motor neurons and causing facial paralysis, also kinesin KIF21A gene
Epidermolysis Bullosa Simplex (EBS)
mutation in keratins, presents as blistering disease that differs in location and severity depending on keratin gene affected; can also be plectin if sensory and muscle involved
Progeria Syndrome
point mutation in prelamin gene, affects post-translational modification in ER where farnesyl group not removed and becomes progerin accumulation instead of nuclear lamin; presents as premature aging; clinical trial of farnesyltransferase inhibitors
Griscelli Syndrome
mutation in myosin V causes delivery of pigments from melanosomes to hair follicle cytoskeleton, presents as silvery sheen in hair, albinism, immunodeficiency; inherited autosomal recessive
Usher Syndrome
autosomal recessive, mutation in myosin VII, hearing loss and retinal pigmentosa
Snell?s Waltzer Mouse
mutation in myosin VI (myo6), presents as vestibular/balance defects
Spinal Muscular Atrophy
mutation in dynein heavy chain
Syndromic Male Sterility
mutation in dynein or nexin in cilia, no crosslinking of adjacent doublets in 9+2 microtubule arrangement, ciliary dyskinesia
Situs Inversus
mutation in flagellar dynein, causing reversal or random organ locations, ciliary dyskinesia, particularly effecting nodal cilia
Charcot-Marie-Tooth Type 2A
mutation in kinesin, presents as peripheral neuropathy
Myasthenia Gravis
autoimmune attack on acetylcholine receptor (AChR), reduced number function of NMJs leads to decreased contraction of muscle and later atrophy
Cystic Fibrosis
improper folding of CFTCR in ER lumen
Role of Integrin in Blood Clot & Cancer
block with RGD tripeptide (Integrillin)
HER2+ Breast Cancer
block with Herceptin
Cardiac Arrythmia
mutation in ankyrin
Proteinuric Kidney Disease
mutation in dynamin involved in pinching off of clathrin-coated pits
Irreversible Sickle Cell Disease
mutation in spectrin involved in maintaining shape of RBC
Duchenne?s Muscular Dystrophy
mutation in dystrophin; MG53 drug shows promise; protein involved in linking laminin of external lamina to actin; progressive muscular weakness; encoded on X chromosome (almost exclusively seen in males). Over time, atrophied muscle fibers invaded by connective tissue
Inherited Deafness
mutation in connexin-26 in gap junctions
Cataracts
mutation in connexin-50 in gap junctions
Kartagener?s Syndrome
type of primary cilia dyskinesia (PCD) caused by absence of dynein arms in normal 9+2 cilia arrangement
Toxic Hepatic Injury
hydropic swelling of hepatocytes leads to enlarged cisternae in ER
Chronic Activation of Unfolded Protein Response (UPR)
causes inflammation in obesity, atherosclerosis, diabetes, and cancer
I-Cell Disease
lysosomal storage disease, deficiency in phosphotransferase in cis-Golgi; can?t add phosphate to mannose; not recognized by M6-P receptor, no delivery to lysosome, disorder of lysosomal biogenesis, no hydrolases in lysosome; accumulation of GAGs and glycolipids; elevated lysosomal enzymes in serum
Clostridium Botulinum
releases toxins that destroy SNARE proteins, affecting exocytosis in neurons and failed contraction in muscle
Familial Hypercholesterolemia
mutation in LDL receptor prevents binding of LDL, used in normal individuals to show clathrin-coated endocytosis via ferritin-labeling
Tay-Sachs Disease
lysosomal storage disease of sphingolipid degradation, accumulation of GM2 ganglioside via deficiency in hexosaminidase-A
Hurler Syndrome
lysosomal storage disorder of GAG degradation, accumulation of dermatan sulfate due to deficiency in alpha-L-iduronidase
Gaucher Disease
lysosomal storage disorder of sphingolipid degradation, accumulation of glucosylceramide due to deficiency in beta-glucocerebrosidase (delivery pathway doesn?t involve M6-P but rather TM protein LIMP-2)
Multiple Myeloma
treatment with proteasome inhibitor Velcade to allow protein build-up in plasma cells which causes cell death
Zellweger?s Syndrome
defect in ability to import proteins into peroxisomes or degradation, build up of LCFA impairs normal function
Adrenoleukodystrophy
impaired beta-oxidation results in accumulation of vLCFA in brain and adrenal gland
Kearns-Sayre Syndrome
abnormalities or deletions in mtDNA affects eye movement, type of mitochondrial myopathy affecting muscles of eye
Mitochondrial disease (mito)
inability to produce enough energy, presents as constant fatigue
Pap Smear
female puberty, hormonal changes cause metaplasia in cervix, but also chance for neoplasia (development of cancerous lesions) so check via pap smear
Bacterial Induced Food Poisoning
diarrhea and dehydration due to disruption of tight junctions between adjacent intestinal epithelial cells; E.coli attacks ZO proteins (PDZ domains) while Clostridium perfringens attacks claudin, massive fluid loss via paracellular pathway
Marfan?s Syndrome
mutation in fibrillin-1 responsible for bundling elastic fibers; long extremities, no pressure on bone due to presence of elastic fibers
Ehlers-Danlos Syndrome
mutation in collagen gene, hyperelastic skin, hypermobility in joings, very fragile blood vessels; ?Rubber Man?
Scurvy
vitamin C/ascorbic acid deficiency, no hydroxylation of proline and lysine residues in collagen presents as poor wound healing and bone formation
Osteopetrosis
disease of malfunctioning osteoclasts, increased bone density but very fragile and break easily; bone formation exceeds resorption
Osteoperosis
insufficient bone mineralization often seen in postmenopausal women; bone resorption exceeds formation; associated with decreased estrogen, which normally inhibits osteoclast activity
Vitamin D Deficiency
decrease in absorption of calcium by intestines, decreased calcium can cause rickets and osteomalacia
Vitamin A
deficiency suppresses endochondral growth of bone while excess leads to fragility and long bone fractures
Acromegaly/Gigantism
over-secretion of somatotropin, involved in stimulating cartilage proliferation and bone growth
Dwarfism
absence or severe hyposecretion of thyroid hormone during development and infancy leads to failure of bone growth
Sickle Cell Anemia
hemoglobin HbS point mutation (glutamic acid … valine) in beta-globin chain gene position 6 chromosome 11; sickled shape cell sticks to walls of blood vessels, especially in smaller capillaries such as those of kidney and brain; heterozygous individual have resistance to malaria, gametocyte of Plasmodium falciparum needs normal Hb inside RBC
Thrombocytopenia purpura
red/purple discoloration of skin, associated with reduction in circulating blood platelets
Primary metastasis
migration/diapedesis from extravascular marrow across sinusoidal epithelium into the blood in leukemia
Rigor Mortis
absence of ATP in muscle cell causes tight binding of myosin-actin (in normal muscle, binding of ATP occurs to induce conformational change and cause uncoupling)
Parkinson?s Disease (PD)
loss of dopamine-secreting cells in substantia nigra and basal ganglia of brain responsible for coordination of smooth and focused skeletal muscle activity
Multiple Sclerosis (MS)
demyelinating disease; slow, rapid loss of function of oligodendrocytes and myelin, unknown etiology; shadow plaques indicate some level of remyelination; autoimmune targeting of myelin basic protein (MBP), produces plaques
Krabbe Disease
autosomal recessive lyososomal storage disease caused by deficiency in lysosomal galactosylceramidase, accumulation of sphingolipids; demyelination, neuronal and muscular atrophy; most cases in infants, Twitcher mouse model
Becker Muscular Dystrophy
partial loss of function of dystrophin (as compared to total LOF in Duchenne MD); also X-linked so almost exclusively found in males
