Unit 2b

Question 1

WAGR Syndrome

Answer 1

Wilms tumor, aniridia, genitourinary malformations, intellectual disability

Question 2

Genetics of WAGR

Answer 2

interstitial 11p13 deletion

-dx with high resolution chromosomal analysis and FISH for PAX6

Question 3

Hereditary Neuropathy with liability to Pressure Palsies (HNPP)

Answer 3

due to deletion of
PMP22 gene leading to a phenotype where patients have temporary (usually reversible)
neuropathy when pressure is applied to various nerves. Just as your arm may go to sleep if
left in a certain position, these patients are more sensitive to pressure on nerves and their
limbs can ‘go to sleep’ for longer periods of time (hours, days, to months)

Question 4

Osteogenesis Imperfecta Type 1

Answer 4

Loss of Function:
Nonsense (stop) mutations / frameshift mutations in
COL1A1  premature termination. Reduced amount of normal COL1A1 (collagen) protein
causing a ‘milder’ form of osteogenesis imperfect. Clinically characterized by increased
fractures, brittle bones, and blue sclera.

Question 5

Hemoglobin Kempsey

Answer 5

Gain of Function:
(Beta hemoglobin gene, Asp99Asn missense mutation): leads to a hemoglobin molecule which has higher than normal oxygen affinity, and is less able to unload oxygen in the tissues.

Question 6

Achondroplasia

Answer 6

FGFR3 Gly380Arg mutation increases the
normal signaling though intracellular tyrosine kinase domain (essentially having the receptor
constitutively in the ‘turned-on’ state).

Question 7

Charcot Marie Tooth

Answer 7

due to duplication of PMP22 gene

also implicted in HNPP above) which leads to elevated PMP22 protein (component of myelin sheath

Question 8

Loss of Function inheritance

Answer 8

typically recessive (one wt copy can usually rescue it)

Question 9

Gain of function inheritance

Answer 9

Gain of function mutations caused by missense are often autosomal dominant (1 improper copy can perform the incorrect function)

Question 10

Huntington Disease

Answer 10

Novel Property:
A triplet repeat disorder where by expansion of CAG
repeat ‘triplets’ in the gene increase the number of glutamine residues (the CAG codon codes
for glutamine). Increased polyglutamine residues above a certain threshold leads to a novel
toxic effect on the huntingtin protein

Question 11

Heterochronic expression mutations

Answer 11

HFPH, some cancers

Question 12

Trinucleotide expansions in non-coding regions (loss of function)

Answer 12

Fragile X, Friedrich Ataxia (mRNA not made, protein not made)

Question 13

Trinucleotide expansions in noncoding regions (novel properties to RNA)

Answer 13

Myotonic Dystrophy, FXTAS (mRNA made but abnormal, protein not made)

Question 14

Trinucleotide expansion in coding regions

Answer 14

Huntington disease, Spinocerebellar ataxia

Question 15

Huntington Expansion

Answer 15

Paternal

Question 16

Myotonoic Dystrophy expansion

Answer 16

maternal anticipation

Question 17

Treat G6PD

Answer 17

No antimalarials

Question 18

treat acute porphyria

Answer 18

No barbiturates

Question 19

Hypercholesterolemia treatment

Answer 19

heterozygotes - oral resins (diversion) and statin drugs (inhibition)
homozygotes- LDL apheresis(depletion)

Question 20

Fabry disease

Answer 20

alpha galactosidase deficiency, treat with Fabryzyme

Question 21

Butyrate

Answer 21

increases expression of fetal hemoglobin, relieving HS

Question 22

Multiple Endocrine Neoplasia

Answer 22

Prophylactic thyroidectomy–>improved survival

Question 23

Progeria treatment

Answer 23

Defect: Lamin AC

Treat Farnesyl transferase

Question 24

Marfans emerging treatment

Answer 24

Defect

Treat Angiotensin II blocker