Quiz 2 Master List Flashcards
Xeroderma Pigmentosum
Cause: defect in nucleotide excision repair leads to the accumulation of thymine dimers
Symptoms: sensitive to direct sunlight, prone to developing melanomas and squamous cell carcinomas
Hereditary Nonpolyposis Colorectal Cancer
Cause: mutation in one of the genes for mismatch excision repair (either MSH2 or MLH1)
Cockayne Syndrome
Cause: defect in transcription coupled repair
Symptoms: neurological and developmental delay, photosensitivity, progeria (premature aging), hearing loss, and eye abnormalities; death usually occurs within the first 2 decades of life
BRCA-associated Breast Cancer
Cause: mutations in BRCA1 or BRCA2 (tumor suppressor genes) that cause a 5-fold increase in a woman’s risk in developing breast and/or ovarian cancer before menopause; men also have an increased risk for breast cancer, as well as pancreatic, testicular, and prostate cancer
Ataxia Telangiectasia (AT)
Cause: defect in the ATM protein, which is a protein kinase that is activated by double-stranded breaks and halts cell division
Familial Hypercholesterolemia
Cause: mutation in gene encoding the LDL receptor; receptors incapable of binding LDL OR bind LDL at reduced capacity OR bind LDL normally but are incapable of internalization
Symptoms: elevated LDL levels, which can lead to atherosclerotic plaques
Zellerger Spectrum Disorders
Cause: defects in the assembly of the peroxisome, most serious being an absence or reduced number of peroxisomes in the cells
Symptoms: present at patients at birth (congenital) and usually causes death within the first year of life
Autosomal Dominant Inheritance
Conditions exhibited in those with 1 copy of the mutant allele; affects males and females equally and any offspring have a 50-50 chance of inheriting the allele
Autosomal Recessive Inheritance
Conditions exhibited in those with 2 copies of the mutant allele; if just 1 is present, individual is a carrier but will not develop the condition; females and males affected equally; if 2 carriers mate, child will have 25% chance of being unaffected, 25% chance of being affected, and 50% chance of being an unaffected carrier
X-linked Dominant Inheritance
When mutation is in father’s X chromosome, all his daughters will express the condition with father-to-son transmission not possible; children of a carrier mother will have a 50% chance of inheriting the mutant allele, but subsequent condition is apparent only if the child has 2 copies of the mutant
X-linked Recessive Inheritance
Conditions not expressed in presence of a normal copy of gene; conditions always expressed in males because they only have 1 X chromosome, but women are rarely affected but can be if they have 2 copies of the mutant or random X-inactivation leaves a tissue vulnerable; never father-to-son transmission but may be father-to-daughter or mother-to-son/daughter transmission
Sickle Cell Anemia
Cause: missense mutation of 6th codon in allele for beta-globin (changes GAG to GTG) which changes glutamic acid to valine
Symptoms: cells have poor oxygen capacity, have sickle cell shape, and tend to clog capillaries, further restricting blood to tissues
Duchenne Muscular Dystrophy
Cause: out-of-frame (frameshift) deletion that results in little to no expression of dystrophin protein
Symptoms: muscle wasting, confined to wheel chair by 12 and death by respiratory failure within 10 years; symptoms onset typically by age 3-5
Becker Muscular Dystrophy
Cause: in-frame (frameshift) deletion that results in truncated forms of dystrophin and gives rise to a milder form of muscular dystrophy
I-Cell Disease
Cause: tagging of lysosomal proteins with mannose-6-phosphate is defective so proteins are not targeted to lysosomes
Symptoms: high plasma levels of lysosomal enzymes; by 6 months, FTT and developmental delays and physical manifestations; development delays of motor skills more pronounced than cognitive delays
Alzheimer’s Disease
Cause: amyloid protein (APP) breaks down to form amyloid beta peptide; misfolding/aggregation of A-beta forms plaques in the brain (extracellular) and hyperphosphorylation of Tau (intracellular)
Symptoms: loss of memory, cognitive function, and language
Parkinson’s Disease
Cause: aggregation of alpha-synuclein (AS) protein forms insoluble fibrils which deposit as Lewy bodies in dopaminergic neurons in substantia nigra
Symptoms: impairment of fine motor control
Huntington’s Disease
Cause: mutation in huntingtin gene results in expression of CAG triple repeats results in polyglutamine repeats in abnormal huntingtin protein
Symptoms: loss of movement and cognitive functions and psychiatric problems
Crutzfeldt-Jacob Disease
Cause: caused by misfolding of prion proteins; TRANSMISSIBLE (infection by misfolded proteins converts normal proteins to misfolded form)
Symptoms: failing memory, behavioral changes, lack of coordination and visual disturbances; late stages involve mental deterioration, blindness, weakness of extremities, and coma
Leber’s Hereditary Optic Neuropathy (LHON)
Cause: 1 of 3 pathogenic mtDNA point mutations affecting NADH dehydrogenase; starves retinal ganglion cells (RGCs) of energy, making them unable to transmit signals to the brain
Symptoms: acute or subacute loss of central vision typically in early teens or 20s; inter-eye delay of 8 weeks
Myoclonic Epilepsy and Ragged Red Fibers (MERRF)
Cause: mutation in the gene encoding for tRNA for lysine, which disrupts the synthesis of cytochrome-c oxidase
Symptoms: patients present with myoclonus dinated muscle movement (ataxia) and seizures; particularly affects muscles and nerves; large variability of presentation due to heteroplasmy
Mitochondrial Encephalopathy, Lactic Acidosis, and Stroke-like Episodes (MELAS)
Most common maternally-inherited mito disease; affects many body systems, particularly brain, nervous system, and muscles
Symptoms: stroke and dementia; diabetes, deafness, cognitive impairment, short stature, migraine
Turner Syndrome
Cause: 45, XO karyotype
Symptoms: short stature, ovarian hypofunction/premature ovarian failure; many do not undergo puberty; most are infertile
Prader-Willi Syndrome
Cause: paternal deletion of a region on chromosome 15
Symptoms: short stature, hypotonia, small hands/feet, obesity, mild to moderate intellectual disability, uncontrolled eating
Angelman Syndrome
Cause: maternal deletion of a region on chromosome 15
Symptoms: severe intellectual disability, seizures, ataxic gait
Klinefelter Syndrome
Cause: 47, XXY karyotype (can also be 48, XXXY or 49, XXXXY)
Symptoms: varying degrees of cognitive, social, behavioral, learning difficulties; primary hypogonadism; small and/or undescended testes; tall stature
Trisomy 21 (Downs Syndrome)
Cause: 47, XX +21 karyotype (most common chromosomal disease) mostly due to maternal meiotic nondisjunction in the ovum
Symptoms: varying degrees of cognitive impairment, structural abnormalities; increased nuchal translucency, cardiac defects, duodenal atresia, ventriculomegaly, absent nasal bone, short limbs
Trisomy 18 (Edwards Syndrome)
Cause: 47, XX +18
Symptoms: microcephaly, prominent occiput, malformed and low-set ears, small mouth and jaw, cleft lip/palate, rocker bottom feet, and overlapped fingers; 95% die in utero
Trisomy 13 (Patau Syndrome)
Cause: 47, XX +13
Symptoms: heart abnormalities, kidney malformations, CNS dysfunction, microcephaly, malformed ears, closely spaced/absent eyes, clenched hands and polydactyl, cleft lip/palate; most die before birth, most perinatal death within 1 week
Pyloric Stenosis
Cause: muscular hypotrophy between stomach and duodenum
Symptoms: leads to vomiting and obstruction; 5 times more common in males than females (males need less ‘risk’ genes to show disease, females need more ‘risk’ genes)
Interesting - children of women with disease are more likely to be born with condition (especially males) and children of men with disease are less likely to be born with condition
Lupus Nephritis
Cause: Complement issue
- immune complexes are formed and deposited in the glomeruli which activates the complement and leads to inflammation
- pro-inflammatory mediators are released, which leads to lesions and tissue fibrosis
Vasculitis
Cause: immune complexes being deposited on the walls of the blood vessels through the classical pathway activation
-common in hep B and hep C patients, SLE
Hereditary Angioedema (HAE)
Cause: deficient in C1 inhibitor
without this, several of the complement proteins are not able to be regulated, which leads to a continuous activation of the complement
C1INH is also responsible for inactivating plasma kallikrein, which produces bradykinin, that will lead to excess swelling
symptoms: edema in various parts of the body mainly hands, feet, and face
abdominal pain, n/v, swelling of the airway in extreme cases
paroxysmal nocturnal hemoglobinuria (PNH)
cause: failure to regulate the formation of the MAC due to a deficiency in the glycosylphosphatidylinositol which allows for the cells to anchor to proteins, such as DAF, and CD59, which are the complement regulators
Without these the complement goes crazy and there is intravascular hemolysis
Ankylosing spondylitis
HLA associated disease: 88% expression the HLA-B27, which may not be able to bind critical antigenic peptides that causes the disease
inflammation of the spine
symptoms: back pain, loss of normal curvature of the back
Rheumatic fever
HLA associated disease: people who do not have the HLA-DR4 are more prone to get RF.
generation of antibodies agains the streptococci which can cross react with cardiac tissue
Sjogren’s syndrome
HLA associated disease; associated with HLA-DR3
defect in salivation and lacrimation (tears)
Insulin Dependent Diabetes Mellitus (Type 1)
HLA-DQ w8
Psoriasis
skin disorder associated with HLA-B3
Bare lymphocyte syndrome
TAP protein is nonfunctional so the peptides are not able to enter the ER (class 1)
Class 1 molecules are not able to leave the ER and then it cannot be expressed by the cells, and there is a “bare” lymphocyte
symptoms: chronic respiratory infections, poor response to viruses
Bare lymphocyte syndrome II
inherited defect in CIITA (CIITA is the transcriptional activator of HLA class II) , which leads to a deficiency of HLA class II expression on cells and non-functioning T lymphocytes
there is decreased class II gene products, which lead to a reduced Th cell count, reduced Ag presentation to CD4 T cells, Decreased humoral and cell mediated responses
Symptoms: severe recurrent infections
What are the transcription factors that are associated with the HLA class II genes?
IFN-y
RFX5
RFXAP
RFXANK
