Autosomal Dominant Diseases

Question 1

*Achondroplasia complete? or incomplete penetrance?

Answer 1

complete penetrance

Question 2

Achondroplasia clinical

Answer 2

autosomal dominant
small stature
Rhizomelic limb shortenieng
short fingers
genu varum
trident hands
large head, frontal bossing
midfacial retrusion
small foramen magnum/ 
craniocervical instability

Question 3

Achondroplasia molecular

Answer 3

FGFR3 mutation
(fibroblast growth factor receptor 3)

• Chr 4p16.3, nu 1138(highest mutation rate known in man), G to A change
• increases regulation of skeletal development

Question 4

Achondroplasia pure or imcompletely dominant?

Answer 4

Imcompletely dominant

-homozygotes affected more than heterozygote

Question 5

*neurofibromatosis type 1 and osteogenesis impoerfecta type 1 are example of

Answer 5

variable expressivity

Question 6

Neurofibromatosis type 1 clinical

Answer 6

• autosomal dominant
• 6 cafe au lait spots
• 2 neurofibromas
• 1 plexiform neurofibroma
• freckling in the axillary or inguinal area
• optic glioma
• 2 lisch nodules
• osseous lesions

Question 7

Neurofibromatosis type 1 molecular

Answer 7

• Autosomal dominant
• mutation NF1
• neurofibromin not working (tumor supressor gene)
• loss of function mutation
• Chr 17q11.2
• need both mutations to show but still dominant

Question 8

Osteogenesis Imperfecta Type 1

Answer 8

• Autosomal Dominant

- 1/30000-50000

Question 9

Osteogenesis Imperfecta clinical

Answer 9

multiple fractures
mild short stature
adult onset hearing loss
blue sclera

Question 10

Osteogensis imperfecta mutation

Answer 10

• mutation COL1A1
• collagen type 1 alpha 1 mut
• Chr 7q21.3
• decreased pro-alpha 1 chain——-> reduce the type 1 collagen by half

Question 11

Marfan Syndrome

Answer 11

Autosomal dominant
1/5000
25% new mutation rate

Question 12

Marfan syndrome clinical

Answer 12

• systemic connective tissue disorder
• ocular disorder
• skeletal disorder
• cardiovascular disorder

Question 13

Marfan syndrome mutation

Answer 13

• FBN1
• reduction in microfibrills
• Chr 15q21.1

Question 14

• Autosomal Dominant Polycystic Kidney Disease info

Answer 14

1/1000 births

5% new mutation rate

Question 15

Autosomal dominant polycystic kidney disease clinical

Answer 15

• bilateral renal cysts
• cysts in other organs
• vascular abnormalities
• end stage renal disease in 50% by 60yrs old

Question 16

Autosomal dominant polycystic kidney disease mutation

Answer 16

PKD1 chr 16p13.3
PKD2 chr 4q22.1 (15%)
Polycystin 1 and 2
truncated protein

Question 17

*Familial Hypercholesterolemia info

Answer 17

Autosomal dominant
1/200-500
very low new mutation

Question 18

familial hypercholesterolemia clinical

Answer 18

• high cholesterol (>310)
• high LDL (>190)
• Xanthomas (cholesterol under skin)
• premature coronary artery disease

Question 19

familial hypercholesterolemia molecular

Answer 19

mutation
LDLK
APO8
PCSK9

Question 20

Huntington Disease info

Answer 20

Autosomal dominant
CAG repeat
1/10000
paternal anticipation

Question 21

Huntington Disease clinical

Answer 21

• progressive neuronal degeneration
• motor, cognitive, psychiatric disturbances
• onset 35-44 yrs old
• death 15 yrs after onset

Question 22

Huntington Disease molecular

Answer 22

mutation HTT
Chr 4p16.3
expansion of glutamine

Question 23

Myotonic Dystrophy Type 1

Answer 23

Autosomal dominant
CTG repeat
(5-34 normal)
(34-49 premutation)
(>50 100% penetrance)
1/20000
maternal anticipation

Question 24

Myotonic dystrophy type 1 clinical

Answer 24

adult onset muscular dystrophy
progressive muscle wasting
myotonia (cannot release grip)
cataracts
aortic coarctation

Question 25

Myotonic dystrophy type 1 molecular

Answer 25

• mutation DMPK
• myotonic dystrophy protein kinase
• Chr 19q13.3
• important for muscle, heart, brain cells