Genetic disorders I

Question 1

autosomal dominant disease display what main features?

Answer 1

1. reduced penetrance 2. variable expressivity 3. delayed onset (possibly) 4. reduced production of protein

Question 2

the gene for marfan syndrome is on which chromosome?

Answer 2

15

Question 3

what protein is defective in marfan syndrome?

Answer 3

fibrillin-1

Question 4

what are the main organs affected by marfan syndrome?

Answer 4

heart, eyes, bone

Question 5

what type of mutation is involved in marfan syndrome?

Answer 5

missense (Cys to Gly)

Question 6

what are the clinical manifestations of marfan syndrome as a result of fibrillin-1 mutations?

Answer 6

stiffening of aortic wall, increased TGF beta activity, inflammation and MMP upregulation, elastolysis and cell disarray

Question 7

what is cystic medial degeneration?

Answer 7

condition caused by marfan syndrome - elastic fiber disruption by pools of blue mucinous ground substance - weakens vessel wall

Question 8

what is the inheritance of marfan syndrome?

Answer 8

autosomal dominant

Question 9

EDS types I and II are characterized by mutations linked to loci that contain which genes? what do they encode?

Answer 9

1. COL5 2. alpha chains and type V collagen

Question 10

what is the histologic appearance of EDS type I?

Answer 10

drop out and clumping of fibers, bear paw patterns

Question 11

NF type 1 is associated with what clinical symptoms?

Answer 11

neurofibromas

Question 12

NF type 2 is associated with what clinical symptoms?

Answer 12

hearing loss and bilateral acoustic neuromas

Question 13

what is the penetrance of NF-1?

Answer 13

100%

Question 14

the NF-1 gene is located on what chromosome?

Answer 14

17

Question 15

what protein is absent in NF-1?

Answer 15

neurofibromin

Question 16

what is the normal function of neurofibromin?

Answer 16

tumor suppressor gene - downregulates the function of the p21 ras oncoprotein

Question 17

what are the clinical symptoms of NF1?

Answer 17

axillary and/or inguinal freckling, cafe au lait macules, lisch nodules, neurofibromas

Question 18

the NF2 gene is located on what chromosome?

Answer 18

22

Question 19

when do patients with NF2 mutation develop symptoms?

Answer 19

around age 60

Question 20

what protein is defective in NF2?

Answer 20

merlin

Question 21

how does NF2 usually present?

Answer 21

hearing deficits, acoustic Schwannomas

Question 22

what are the features of the biphasic pattern of schwannomas?

Answer 22

1. antoni A - more fibrosis within tumor, more cellular, more dense collagen 2. antoni B - more mixoid CT, less dense

Question 23

what are verocay bodies?

Answer 23

palisading tumor cells with dense CT between them