32: Genetic diseases I

Question 1

what do these diseases have in common: marfan, ehler-danlos, achondroplastic dwarfism, ostoegenesis imperfecta

Answer 1

quantity or arrangement of large structural proteins

autosomal dominant

Question 2

what do these diseases have in common: hutington, famililial hypercholesterolemia

Answer 2

reugator proteins and receptors

autosomal dominant

Question 3

4 categories of autosomal dominant diseases

Answer 3

1. quantity of arrangement of large structual proteins
2. regulatior proteins and receptors
3. deficiency in proteins that are in short supply even in health
4. anti-oncogene deletion syndormes

Question 4

defect of connective tissue with faulty scaffolding due to mutation in gene on chromosome 15 which encodes for fibrillin-1

Answer 4

marfan syndrome

Question 5

where is fibrilin found

Answer 5

• aorta
• suspensory ligamne tof lensy
• periosteum

Question 6

how does bone overgrowth occur in marfan syndrome?

Answer 6

the periosteum is more elastic than it should be and doesnt provide enough oppositional force, overgrowth of bone occurs

Question 7

what type of mutation is marfan syndrome

Answer 7

missense mutation in fibrilin gene on chromosome 15

Question 8

inheritance pattern of marfan syndrome

Answer 8

autosomal dominant

Question 9

occurance of marfan syndrome

Answer 9

1/10,000 north americans

Question 10

ectopia lentis

pigeon chest or hollwo chest

spider fingers

mitral valve prolapse

Answer 10

characteristics of marfan syndrome

Question 11

dolichostenomelia

Answer 11

unusually long and slender limbs associated with marfan syndrome

Question 12

frequent cause of death for marfan patients

Answer 12

congestive heart failure

Question 13

ectopia lentis

Answer 13

due to lax suspensory ligaments of the lens with marfan syndrome

–>nearsightedness

Question 14

hollow chest

Answer 14

pectus excavatum

Question 15

pigeon chest

Answer 15

pectus carinatum

Question 16

elastic fibers, instead of running in parallel arrays are disrupted by pools of blue mucinous ground susbstance

Answer 16

cystic medial degeneration associated with marfan syndrome

Question 17

quantitative or qualitative abnormalities in collagen synthesis

Answer 17

ehlers danlos syndromes

Question 18

mutations linked to loci that contain the COL5A1 or COL 5A@ genes encoding the alpha chains of type V collagen

Answer 18

types I and II classical EDS

Question 19

decreased amount of type III collagen (reticulin)

Answer 19

type IV EDS

Question 20

deficiencis in lysyl hydroxylase and lysyl oxidase and important modifying nezyme in collagen biosynthesis

Answer 20

types V and VI EDS

Question 21

amino-terminal procollagen peptidase deficiency ( cannot turn procollagen into collagen)

Answer 21

type VII EDS

Question 22

most deadly EDS

Answer 22

type IV EDS

Question 23

which EDS are autosomal recessive?

Answer 23

VI and VIIc

All the others are autosomal dominant

Question 24

what is the frequency of EDS III? EDS I/II?

Answer 24

III= 1/5000

I/II = 1/30,000

Question 25

collagen pathway: prevents secretion

Answer 25

vascular IV EDS

Question 26

collagen pathway: reduction in col5AI mRNA

Answer 26

classic EDS I/II

Question 27

collagen pathway: prevents cleavage

Answer 27

athrochalasia VIIa,b | EDS

Question 28

rubber man

Answer 28

EDS type I

Question 29

bear paw collagen

Answer 29

EDS type I

Question 30

beighton scale for joint hypermobility

Answer 30

a total score of at least 5 define hypermobility

Question 31

kyphoscoliosis

Answer 31

type VI EDS

Question 32

congential hip dislocation

Answer 32

type VII a, b EDS

Question 33

uterine rupture, posterior tibial artery rupture

Answer 33

type IV EDS

Question 34

incidence of NF1

Answer 34

1/3000 highly variable expression but 100% penetrance

Question 35

about __ of NF1 cases are new mutations

Answer 35

50%

Question 36

NF1 gene encodes for

Answer 36

tumor suppressor prtn neurofibromin which down regulates the function of p21 ras oncoprotein (converts active ras to inactive ras-GDP)

Question 37

axillary of inguinal feckling cafe-au-lait macules lisch nodules neurofibromas

Answer 37

NF1

Question 38

two or more of the follwoing bust be present for NF1 diagnosis

Answer 38

1. 6 CALM 2. freckling in armpits or groin area 3. 2 or more neurofibromas or 1 plexiform neurofibroma 4. more than 2 lisch nodules 5. optic glioma 6. bone lesions 7. first degree relative diagnosed with NF

Question 39

pigmented hamartomas of the iris

Answer 39

lisch nodules

Question 40

cell of origin for neurofibroman

Answer 40

schwann cell

Question 41

persons with neurofibromatosis have a long-term risk for development of malignant neoplasms -->

Answer 41

malignant peripheral nerve sheath tumors

Question 42

NF1 v. NF2

Answer 42

separate entities with localization of the respective genes to chromosomes 17q (NF1) and 22q (NF2) both are autosomal dominant

Question 43

subjects who inherit a pathogenic mutation in the NF2 gene will almost always develop symptoms by ____- yo

Answer 43

60 years old

Question 44

NF2 gene product

Answer 44

tumor suppressor merlin/schwannomin --> NF-2 associated and sporadic tumors if inactivated

Question 45

bilarteral vestibular schwannomas (acuoustic neruomas) and meningiomas

Answer 45

NF2

Question 46

manchester crtieria

Answer 46

for clinical diagnosis of NF2

Question 47

presentation of NF2 patient

Answer 47

hearing loss with tinnitus, dizziness or imbalance --> become deaf

Question 48

bunch of grapes tumor

Answer 48

NF2

Question 49

biphasic appearance of schwannoma

Answer 49

antoni A/B and verocay bodies associated with NF2