Genetic

Alport Syndrome
Cause: mutation in genes related to collagen biosynthesis
Reason: the proteins mutated are responsible for type IV collagen production and
assembly, a type of collagen that is important in basement membranes. Particularly, the
kidney, inner ear, and eye are heavily affected.
Result: The basement membranes are unable to filter waste, blood, ions, and gasses
properly. In the kidney the glomerulonephritis results in blood and proteins in the urine.
Long term damage can result in kidney failure. Other features include progressive hearing
loss and eye abnormalities (ocular lesions)
Treatment: no cure and treatment is focused on the symptoms. ACE inhibitors are
provided, along with dialysis or potential kidney transplant.
Bullous Pemphigoid
Cause: autoimmune
Reason: antibodies are created against hemidesmosome proteins
Result: The epithelial layer is unable to stay adhered to the connective tissue below and
fluid fills the space to form a blister. Early symptoms resemble hives and include burning
and itching sensations
Treatment: corticosteroids or immunosuppresants
Charcot-Marie Tooth disease
Cause: X-linked dominant disease affecting the production of Connexin-32
Reason: connexin-32 is a gap junction protein found between layers of myelin sheath in the
peripheral nervous system. The lack of gap junctions results in diminished gas, nutrient, and
ion transfer. Demyelination follows, exposes the axon to damage, and leads to neuropathy.
Result: progressive loss of muscle weakness and muscle tissue, along with loss of touch
sensation
Treatment: No cure, treatment involves physical therapy to maintain strength
Other: related pathologies include connexin-50 defect resulting in cataracts, and connexin-
26 defect resulting in deafness
Cockayne Syndrome
Cause: autosomal recessive, mutations in the ERCC6 and ERCC8 genes
Reason: DNA repair system (coupled to transcription) is slowed down greatly (when an RNA
poly halts while transcribing, this repair system comes in to fix the DNA), leading to an
accumulation of DNA damage
Result: the syndrome is characterized by failure to thrive, short stature, premature aging,
microcephaly, impaired development of the nervous system, and a sensitivity to sunlight
Treatment: There is no cure for this syndrome and treatment focuses on the symptoms.
Other: not associated with cancer, although no one knows why
Cystic Fibrosis
Cause: autosomal recessive genetic mutation, over 700 of which have been associated with
cystic fibrosis
Reason: The Cystic Fibrosis Transmembrane Conductance Regulator (CFTR) protein is
inactivated. The protein is involved in production of several fluids, including sweat,
digestive fluid, and mucus. Dysfunctional CFTR results in a thickening of these fluids, causing
multi-system symptoms.
 Result: Most notably difficulty breathing and frequent lung infections. Other symptoms
include problems with the pancreas, kidneys, liver, and intestines. Clubbing of fingers,
stunted growth, sinus infections, and infertility in males is also seen.
Treatment: There is no cure and treatment is focused on controlling infections and
symptoms. Antibiotics for infections, enzyme replacement for pancreas, and potential lung
replacements are options.
Duchenne's Muscular Dystrophy
Cause: X-linked recessive (affects 1/3600 males starting at a young age)
Reason: absence of dystrophin, a protein in skeletal muscles that anchors the actin fibers to
the cell membrane. Structural integrity compromised and Ca2+ begins to leak out,
activating proteases that further damage the muscle
Result: Progressive muscle weakness eventually leading to loss of movement, skeletal
deformities, and paralysis
Treatment: No cure, but treatment, including physical therapy and corticosteroids, is aimed
at controlling symptoms and maximizing quality of life
Ehler's Danlos Syndrome type I and type II
Cause: mutations in several fibrous proteins and enzymes results in a defective Type V
collagen
Reason: Type V collagen defect results in impaired collagen fibril formation which in turn
leads to compromised support and strength in skin, muscle, joints, and blood vessels.
Result: fragile skin, hypermobile joints, weak arteries prone to eruption
Treatment: no cure, treatment focuses on support
Hemoglobin Cranston
Cause: spontaneous mutation
Reason: two nucleotide addition to the beta globin gene, causing a frameshift that
eliminates the original stop codon
Result: the beta hemoglobin protein extends from a normal of 146 AA to 157 AA, resulting in
an unstable beta globin protein
Treatment: N/A
Hutchinson-Gilford Syndrome
Cause: single nucleotide mutation (C1824t) to LMNA gene
Reason: Lamin A, a scaffolding molecule for the nucleus, is mutated. The new protein,
called progerin, has 50 amino acids missing and disrupts the shape of the nuclear envelope.
Result: premature aging signs at 6 months - 1 year of age. Baldness, prominent scalp, small
jaw, thin limbs with prominent joints, short stature, joint stiffness, and tight, shiny skin. Life
expectancy of 13 years.
Treatment: no cure exists, treatment involves improving the quality of life
Kniest Dysplasia, achrondrogenesis type 2
Cause: genetic mutation in the gene for Type II Collagen
Reason: Type II collagen is most commonly found in cartilage, but is also found in the
vitreous humor of the eyeball.
Result: short stature, restricted joint mobility, blindness, wide metaphyses, joint
abnormalities, and dwarfism, cleft lip
Treatment: N/A
Marfan Syndrome
Cause: autosomal dominant mutation in FBN1 gene
Reason: FBN1 gene encodes for fibrillin-1, a protein that is important in the organization of
elastin into fibers - mainly found in vertebral ligaments, larynx, and elastic arteries
 Result: tall stature and long limbs, enlargement of the base of aorta to compensate for weak
arteries, extreme nearsightedness, and curved spine. In extreme cases the arteries can tear
away from the heart due to high pressure
Treatment: surgical aid
Multiple Sclerosis
Cause: autoimmune
Reason: a progressive demyelination of axons in the central nervous system
Result: progressive physical weakness, neurological and psychiatric problems
Treatment: a cure does not exist, and current treatments focus on improving function after
an attack or in prevention of progression
Other: most common autoimmune disorder, mostly affects women
Myasthenia Gravis
Cause: autoimmune
Reason: antibodies block acetylcholine receptors (nicotinic cholinergic) at the
neuromuscular junction
Result: muscle weakness and fatigue, can affect different muscles and are classified
accordingly
Treatment: acetylcholinesterase inhibitors, immunosuppressive therapies in some cases
Other: about 3-30 cases per 1 million per year
Niemann-Pick Disease Type A and B
Cause: mutation in the SMPD1 gene
Reason: inability to make sphingomyelinase, resulting in an accumulation of sphingomyelin
in cells
Result: Type A (classic/infantile) results in jaundice caused by an enlarged liver and nervous
system degeneration. Type B (visceral) results in hepatosplenomegaly, impaired lung
function and blood abnormalities. The nervous system is preserved in Type B. In type A the
individual has a life expectancy of 18 months, whereas for type B it is possible for individuals
to have a near normal life expectancy
Treatment: no treatment exists for Type A, but type B is manageable with treatment of
symptoms. Enzyme replacement and gene therapy is also a future possibility
Osteogenesis Imperfecta
Cause: mutation in gene for type I collagen
Reason: type I collagen is the main substance found in tendons, ligaments, bones, and a lot
of connective tissue. A defective type I collagen can lead to all of these tissues being
imperfect
Result: most commonly brittle bone with repeated fractures, abnormal teeth, thin skin,
weak tendons, and progressive hearing loss
Treatment: No cure, and treatments focus on strengthening bones and maintaining mobility
Primary Ciliary Dyskinesia
Cause: autosomal recessive
Reason: mutation causes a defect in the dynein arms of cilia, compromising the motility of
cilia
Result: areas where cilia is located are compromised, namely the respiratory tract which
would become unable to efficiently remove mucus, leading to respiratory infections. Other
affected regions include the fallopian tubes and the flagella of sperm cells.
Treatment: Antimicrobials for bacterial infections
Sickle Cell Anemia
Cause: hereditary mutation in the beta globin gene
 Reason: single nucleotide missense mutation (base pair replacement) causes a glutamic
acid (polar) at position 6 to change to valine (hydrophobic)
Result: causes red blood cells to adopt a sickle shape, resulting in reduced oxygen transport.
The condition is associated with multiple chronic health problems such as severe infections,
sickle cell crisis, clots and stroke.
Treatment: complications of sickle cell disease can be prevented by antibiotics, blood
transfusion, vaccination, and hydroxyurea
Werner Syndrome
Cause: Mutation to WRN gene
Reason: WRN protein, a helicase and exonuclease, is abnormally short and is not
transported into the cell nucleus
Result: premature aging beginning around puberty, resulting in an appearance of old age
around 30-40 years old. Death usually ensues by age 50 from heart disease or cancer
Treatment: no cure exists, treatment involves improving the quality of life
Xeroderma Pigmentosa
Cause: autosomal recessive genetic disease
Reason: nucleotide excision repair enzymes are mutated, resulting in an inability to fix UV-
induced thymine dimers
Result: an extreme sensitivity to UV radiation leading to an intolerance for sunlight. Skin
cancer frequently occurs at a young age (2000x risk) and is often the cause of death.
Treatment: No cure exists, and treatment includes avid avoidance of sunlight.
Other: Individuals with XP are colloquially called "Children of the Night"

Bacterial
Botulinum toxin
Cause: Clostridium botulinum, an anaerobic bacteria
Reason: Botulinum toxin cleaves SNARE proteins in vesicles, preventing their exocytosis
from presynaptic nerve cells. This prevents neurotransmitter (acetylcholine) release
Result: Paralysis of muscles; at high doses it is fatal as it can paralyze the diaphragm and
cause acute respiratory failure
Treatment: induce vomiting and bowel movement to get the bacteria and toxin out of the
GI. An antitoxin exists to negate the toxin but nerves already affected require months to
regrow and requires extended physical therapy. Antibiotics for the bacteria
Other: can be medically used to weaken a muscle for several months; botox injections
paralyze facial muscles and prevent development of wrinkles. Other derivatives such as
curare (paralyzes skeletal muscles) and succinyl choline (muscle relaxant for emergency
purposes) exist.
Cholerae Toxin
Cause: Vibrio Cholerae, gram negative bacteria
Reason: Cholerae toxin inactivates a GTPase that would normally terminate a receptor
signaling. This results in constant cAMP (a secondary messenger) production and leads to
massive secretions of ions (Na+, K+, Cl-, HCO3-). Water follows out into the lumen of the GI
due to differences in osmolarity, resulting in severe dehydration and diarrhea.
Treatment: antibiotics, continued eating and hydration to replace ions and water loss.
Vaccines are also available.
Diphtheria toxin
Cause: Corynebacterium diphtheriae
 Reason: diphtheria toxin inactivates eEF2 via ADP ribosylation. This has the consequence of
preventing elongation during translation of mRNA to a polypeptide chain.
Result: Starting with fever and sore throat, a grey or white patch develops in the throat and
can block the airway, leading to a "barking cough." The neck may swell up due to enlarged
lymph nodes. Complications may include myocarditis, inflammation of nerves, kidney
problems, and bleeding issues.
Treatment: diphtheria vaccine exists. Treatment includes erythromycin or penicillin D.
Tracheostomy in severe cases.
Tetanus
Cause: Clostridium tetani
Reason: tetanus toxin is taken up at an open wound and travels through the peripheral
nervous system until it reaches the central nervous system. There, it inhibits the release of
inhibitory neurotransmitters (GABA and glycine) by degrading SNARE complexes
Result: muscle spasms in the skeletal muscles (not in cardiac muscle because they have their
own intrinsic electrical system, secondary symptoms include fever, sweats, headache,
trouble swallowing, high blood pressure, and a fast heart rate
Treatment: tetanus vaccine and tetanus Ig, muscle relaxants and in dire situations a
mechanical ventilator
Other: non-transferrable, obtained usually from puncture wound with infected object

Miscellaneous
Guillain-Barre Syndrome
Cause: Autoimmune reaction post infection against the Peripheral Nervous System
Reason: During an infection antibodies are produced to fight foreign bodies. In a concept
known as molecular mimicry, the resultant antibodies also react against substances
naturally occurring in the body, in this case against human nerve cell gangliosides
Result: Inflammation and demyelination of peripheral nerve cells, resulting in reduced
conductance and axonal damage. Symptoms include rapid onset muscle weakness and
changes in sensation and pain. Fatal cases involve weakness in respiratory muscles, and
changes in the function of the autonomic nervous system.
Treatment: intravenous immunoglobulins, plasmapheresis, and supportive care
Other: Incidence of 1/100,000 per year; classified as an acute polyneuropathy

*No genetics lecture stuff, will make another list later

**Does not include general clinical correlations, like chronic asthma, reactive lymphadenitis, etc
***Also does not include Aging