Mutational Diseases

Question 1

Loss of function mutation disorders

Answer 1

• Duchenne muscular dystrophy
• alpha thalassemia
• turner syndrome
• hereditary neuropathy with liability to pressure palsies
• osteogenesis imperfecta type 1

Question 2

Duchenne muscular dystrophy (DMD)

Answer 2

• Loss of function
• multiple exon deletion, x linked,Xp21.1
• nonsense mutations/
• frameshift mutations( MAJOR)
  _**in-frame deletion (missense)—–>milder becker muscular dystrophy (reduction function, mild form of DMD)

-abnormal gait at 3-5 yrs old
- Calf pseudohypertrophy
- Gower maneuver
- respiratory muscles usage
- 18 yrs old death
women —->cardiomyopathy

Question 3

Hereditary neuropathy with liability to pressure palsies (HNPP)

Answer 3

• Loss of function,
• Autosomal Dominant
• Deletion of PMP22 gene (glycoprotein in nerves)
• repeated focal pressure neuropathy
• reversible neuropathy
• incomplete recovery—>mild disability

Question 4

Osteogenesis imperfecta type 1

Answer 4

• Loss of function
• Autosomal Dominant
• nonsense and frameshift at COL1A1 gene

Brittle bones, blue sclerae, normal stature.
progressive hearing loss

Question 5

Hemoglobin Kempsey

Answer 5

• gain of function
• Beta hemoglobin gene- Asp99Asn missense
• Relaxed state= gain of function (high affinity)
• unloads less O2
• more red blood cell production—> polycythemia

Question 6

Charcot Marie Tooth Syndrome Type 1A (CMT1A)

Answer 6

• Gain of function
• Autosomal dominant
• duplication of PMP22 gene–> more PMP22 proteins
• demylination
• lower extermity weakness
• muscle atrophy
• mild sensory loss

Question 7

Sickle cell anemia

Answer 7

novel property mutation

• no change in O2 carrying ability
• **polymerization in low O2
• long polymer= sickle cell shape

Question 8

Osteogenesis Imperfecta Types 2,3,4

Answer 8

novel property mutation

• make abnormal collagen trimers
• ** more detrimental than type 1 with half normal trimer.

Question 9

Hereditary Persistence of Fetal Hemoglobin (HPFH)

Answer 9

expression mutation
deletion of beta hemoblobin locus
retention of gamma-globin gene

Question 10

Huntington Disease

Answer 10

Trinucleotide Repeats
CAG
more than 40--->onset, toxic glutamine
paternal expansion
slipped misparing during DNA replication

Question 11

Myotonic dystrophy

Answer 11

Trinucleotide Repeats
CTG
maternal expansion
slipped misparing during DNA replication

Question 12

Myotonic dystrophy mild

Answer 12

catracts, mild myotonia
50 -150 repeats
20yrs - 70yrs onset
average 60 yrs life

Question 13

Myotonic dystrophy classic

Answer 13

weakness, myotonia, cataracts, bolding

• 100 -1000 repeats
• 10 to 30 yrs onset
• 48 to 55 yrs life

Question 14

Myotonic dystrophy congenital

Answer 14

Infantile hypotonia, 
respiratory deficits, 
intellectual disability, 
>2000 repeats
-Birth to 10 yrs onset
- 45 yrs life