Quiz 2 Master List

Question 1

Xeroderma Pigmentosum

Answer 1

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

Question 2

Hereditary Nonpolyposis Colorectal Cancer

Answer 2

Cause: mutation in one of the genes for mismatch excision repair (either MSH2 or MLH1)

Question 3

Cockayne Syndrome

Answer 3

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

Question 4

BRCA-associated Breast Cancer

Answer 4

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

Question 5

Ataxia Telangiectasia (AT)

Answer 5

Cause: defect in the ATM protein, which is a protein kinase that is activated by double-stranded breaks and halts cell division

Question 6

Familial Hypercholesterolemia

Answer 6

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

Question 7

Zellerger Spectrum Disorders

Answer 7

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

Question 8

Autosomal Dominant Inheritance

Answer 8

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

Question 9

Autosomal Recessive Inheritance

Answer 9

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

Question 10

X-linked Dominant Inheritance

Answer 10

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

Question 11

X-linked Recessive Inheritance

Answer 11

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

Question 12

Sickle Cell Anemia

Answer 12

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

Question 13

Duchenne Muscular Dystrophy

Answer 13

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

Question 14

Becker Muscular Dystrophy

Answer 14

Cause: in-frame (frameshift) deletion that results in truncated forms of dystrophin and gives rise to a milder form of muscular dystrophy

Question 15

I-Cell Disease

Answer 15

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

Question 16

Alzheimer’s Disease

Answer 16

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

Question 17

Parkinson’s Disease

Answer 17

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

Question 18

Huntington’s Disease

Answer 18

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

Question 19

Crutzfeldt-Jacob Disease

Answer 19

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

Question 20

Leber’s Hereditary Optic Neuropathy (LHON)

Answer 20

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

Question 21

Myoclonic Epilepsy and Ragged Red Fibers (MERRF)

Answer 21

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

Question 22

Mitochondrial Encephalopathy, Lactic Acidosis, and Stroke-like Episodes (MELAS)

Answer 22

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

Question 23

Turner Syndrome

Answer 23

Cause: 45, XO karyotype

Symptoms: short stature, ovarian hypofunction/premature ovarian failure; many do not undergo puberty; most are infertile

Question 24

Prader-Willi Syndrome

Answer 24

Cause: paternal deletion of a region on chromosome 15

Symptoms: short stature, hypotonia, small hands/feet, obesity, mild to moderate intellectual disability, uncontrolled eating

Question 25

Angelman Syndrome

Answer 25

Cause: maternal deletion of a region on chromosome 15

Symptoms: severe intellectual disability, seizures, ataxic gait

Question 26

Klinefelter Syndrome

Answer 26

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

Question 27

Trisomy 21 (Downs Syndrome)

Answer 27

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

Question 28

Trisomy 18 (Edwards Syndrome)

Answer 28

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

Question 29

Trisomy 13 (Patau Syndrome)

Answer 29

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

Question 30

Pyloric Stenosis

Answer 30

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

Question 31

Lupus Nephritis

Answer 31

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

Question 32

Vasculitis

Answer 32

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

Question 33

Hereditary Angioedema (HAE)

Answer 33

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

Question 34

paroxysmal nocturnal hemoglobinuria (PNH)

Answer 34

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

Question 35

Ankylosing spondylitis

Answer 35

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

Question 36

Rheumatic fever

Answer 36

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

Question 37

Sjogren’s syndrome

Answer 37

HLA associated disease; associated with HLA-DR3

defect in salivation and lacrimation (tears)

Question 38

Insulin Dependent Diabetes Mellitus (Type 1)

Answer 38

HLA-DQ w8

Question 39

Psoriasis

Answer 39

skin disorder associated with HLA-B3

Question 40

Bare lymphocyte syndrome

Answer 40

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

Question 41

Bare lymphocyte syndrome II

Answer 41

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

Question 42

What are the transcription factors that are associated with the HLA class II genes?

Answer 42

IFN-y
RFX5
RFXAP
RFXANK