CMB Exam 1 - Diseases

Question 1

Zellweger syndrome

Answer 1

Mutation in the PTS1, PTS2, or Pex genes. Lethal within first decade of life

Question 2

systemic lupus erythematosus (SLE)

Answer 2

Antibodies against U1, U2, U4, U5 snRNPs.

Question 3

Huntington’s Disease

Answer 3

Expansion of CAG repeat in excess of 36 copies of brain-expressed gene.

Question 4

Cholera Toxin

Answer 4

ADP-ribosylates Gs unit of GPCR recepter, rendering it continually active which leads to continuous cAMP production. Leads to massive water loss through the intestines

Question 5

Pertussis

Answer 5

ADP-ribosylates Gi unit of GPCR recepter, rendering it continually inactive which leads to continuous cAMP production (its usual function is to inhibit cAMP production). Leads to loss of Cilia in respitory tract, inability to expel mucous = whooping cough.

Question 6

Rett Syndrome

Answer 6

X-linked dominant mutation of MeCP2 (protein that binds methylcytosine in DNA to repress translation). Develop normally for 1-2 years, then lose motor and cognitive skills: mental deficiency, autism, repetitive hand movements, and/or autonomic dysfunction. Death between 12 and 50 years. High variability in phenotype.

Question 7

xeroderma pigmentosum (XP)

Answer 7

Results from lost ability to perform nucleotide-excision repair (mutated XPA-XPG products). Presents with cutaneous photosensitivity.

Question 8

Cockayne’s syndrome

Answer 8

Deficent CsB protein (transcription-coupled nucleotide-excision repair). Poor growth, neurological degeneration, and early senility.

Question 9

hereditary nonpolyposis colon cancer

Answer 9

Defective proteins of post-replication mismatch repair

Question 10

ataxia-telangiectasia

Answer 10

Deficient checkpoint proteins (ATM). Presents with loss of motor coordination, immune deficiency, chromosome breaks, lymphomas, leukemia.Mutat

Question 11

fragile-x syndrome

Answer 11

X-linked dominant disease in individuals with over 200 CGG repeats in the FMR1 gene (too many repeats leads to inactivation by methylation). 50% penetrance in females, 90% in males. Most common form of inherited retardation in males. SSX: mental retardation and stereoypical phenotype, heart problems, enlarged testes, skin problems. Anticipation effect.

Question 12

retinitis pigmentosum

Answer 12

Incorrect folding of rhodopsin ultimately leads to apoptosis of rods and night blindness. Protein is retained in ER/Golgi, never sent to membrane.

Question 13

I-cell disease

Answer 13

Deficiency in enzyme catalyzing the first step in tagging lysosomal enzymes with M6P in the golgi. Lysosomal enzymes are erroneously secreted into the serum.

Question 14

Creutzfeldt-Jacob disease

Answer 14

Non-transmittable (among humans) spongiform encephalopathy. Prions.

Question 15

Variant CJD

Answer 15

“Mad cow”. Transmittable spongiform encephalopathy. Prions

Question 16

kuru

Answer 16

Transmittable spongiform encephalopathy (from eating dead family members’ brains). Prions.

Question 17

competitive antagonism between O2 and CO

Answer 17

Hb binds CO 200 times more tightly than O2. 30%-50% CO saturation leads to: headache, confusion, and fainting. 80% CO saturation is fatal. Overcome by elevating pO2.

Question 18

Tay-Sachs disease

Answer 18

Deficiency in the hexosaminidase A enzyme leads to errant metabolism of lipids, forming the “Tay Sachs ganglioside”. Accumulated lipid: Cer-Glc-Gal(NeuAc):GalNAc GM2 ganglioside

Question 19

Gaucher’s disease

Answer 19

Lysosomal storage disorder. Deficiency in the beta-glucosidase (aka glucocerebrosidase) enzyme results in the accumulation of glucosylceramides in the lysosomes. Common in Jewish populations (1:2500)

Question 20

LHON

Answer 20

(Leber’s hereditary optic neuropathy) Rare inherited disease causing optic nerve degeneration, caused by mutation in mitochondrial DNA that codes for NADH dehydrogenase. Since this reduces ATP capacity, CNS and optic nerve suffer most. Incomplete penetrance.

Question 21

Li Fraumeni syndrome

Answer 21

Results from defective checkpoint proteins Chk2 and/or p53. Presents with motor in coordination, immune deficiency, chromosome breaks, lymphomas.

Question 22

retinoblastoma

Answer 22

Two hits required, one inherited and one spontaneous mutation in retinal cells.

Question 23

neurofibromatosis

Answer 23

Condition with variable phenotype ranging from cafe au lait spots (abnormal pigmentation) to cancerous growths, ADHD, hypertension, learning disabilities, reduced stature, large head, etc. Peiotropic.

Question 24

sickle cell disease

Answer 24

Autosomal recessive condition common in black populations (1:12 allelic frequency, 1:500 disease frequency).

Question 25

SCID

Answer 25

(severe combined immune disorder) X-linked recessive.

Question 26

hemochromatosis

Answer 26

Autosomal recessive mutation of the HFE gene resulting in iron overload, 35%-40% penetrance

Question 27

fragile-x syndrome

Answer 27

X-linked dominant disease in individuals with over 200 CGG repeats in the FMR1 gene (too many repeats leads to inactivation by methylation). 50% penetrance in females, 90% in males. Most common form of inherited retardation in males. SSX: mental retardation and stereoypical phenotype, heart problems, enlarged testes, skin problems. Anticipation effect.

Question 28

cystic fibrosis

Answer 28

Autosomal recessive disorder with over 1000 diff pathogenic variants of CFTR gene (allelic heterogeneity)

Question 29

nonsyndromic deafness

Answer 29

Inherited deafness, can be either autosomal dominant or recessive. Locus heterogeneity.

Question 30

familial hypercholesterol

Answer 30

Autosomal dominant defect in the LDLR gene (normally removes LDL from circulation). 20%-40% affected individuals present with xanthelasma palpebrarum, arcus senilis cornea, and/or tendon xanthoma, while others show no symptoms (incomplete penetrance). 85% of men have heart attack by 60, women by 70.

Question 31

xanthelasma palpebrarum

Answer 31

Cholesterol accumulation around the eyelids, often due to familial hypercholesterolemia

Question 32

arcus senilis cornea

Answer 32

Cholesterol accumulation within the iris, often due to familial hypercholesterolemia.

Question 33

tendon xanthoma

Answer 33

Cholesterol accumulation in the tendons of the hands, feet, elbows or knees. Often related to familial hypercholesterolemia.

Question 34

color blindness

Answer 34

x-linked recessive, affects 8% males of european decent, 0.5% females

Question 35

Huntington’s disease

Answer 35

Trinucleotide repeat causes proteins to aggregate and kill brain cells. Lethal by middle age.

Question 36

MERRF

Answer 36

(myoclonic epilepsy with ragged red fibers) mtDNA disease

Question 37

Patau syndrome

Answer 37

trisomy 13

Question 38

Edwards syndrome

Answer 38

trisomy 18

Question 39

Turner syndrome

Answer 39

lone X chromosome

Question 40

22q11 deletion syndrome

Answer 40

Autosomal dominant deletion on chromosome 22 affecting 1:68 individuals with congenital heart defects (associated with truncus arteriosus and tetralogy of Fallot). Can cause cleft palate, learning disabilities, hypocalcemia, etc.

Question 41

15q11-13 deletion

Answer 41

Causes either Prader-Willi syndrome or Angelman syndrome, depending on whether it was inherited from the father or the mother, respectively.

Question 42

Prader-Willi syndrome

Answer 42

Caused by a 15q11-13 deletion inherited from dad (imprinting). SSX: obesity, insatiable appetite, hypotonia, infertility, other physical manifestations (almond eyes, downturned mouth, thin upper lip, soft light skin, small hands and feet, flattened ulnar border).

Question 43

Angelmann syndrome

Answer 43

Caused by a 15q11-13 deletion inherited from mom (imprinting). SSX: excessive smiling/laughing, speech impairment, wide mouth and wide-spaced teeth, movement disorders, crave social interaction.

Question 44

FAP

Answer 44

(familial adenomatous polyposis) mutation in the APC (a. dominant) or MUTYH (a. recessive) genes cause colon polyps age 39-55.

Question 45

HNPCC (Lynch syndrome)

Answer 45

Autosomal dominant disease caused by mutations in 1 of 5 genes; causes up to 5% of all colorectal cancers.