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Flashcards in Autosomal dominant Deck (71)
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1

Achondroplasia
inheritance

autosomal dominant

2

Achondroplasia
incidence

1/15,000-40,000

3

Achondroplasia
mutation rate?

80%

4

Achondroplasia
penetrance?

100%

5

Achnodroplasia
Clinical manifestations

Short
Rhizomelic limb shortening (proximal shortening)
short fingers
genu varum (bow legs)
large head / frontal bossing
midfacial retrusion
small foramen magnum / craniocervical instability

6

Achondroplasia
Mutated gene?

FGFR3
Fibroblast growth factor receptor 3

7

What does FGFR3 do?

Regulates bone growth by limiting the formation of bone from cartilage

8

FGF43 locus?

4p16.3 nucleotide 1138

9

Achondroplasia mutation?

nucleotide 1138 missense
1138G>A
amino acid substitution
Gly380Arg

10

Achondroplasia mutation consequence

Mutation increases the activity of the protein, interfering with skeletal development

11

What is special about the achondroplasia mutation 1138

The 1138 of FGFR3 has the highest known mutation rate in man

12

Men and de novo autosomal dominant conditions?

Men over the age of 40 are noted to have hgiher rate of children with de-novo autosomal dominant conditions - i.e. Achondroplasia

13

Paternal age effect

old dudes yield autosomal dominant mutated sperm

14

4 syndromes associated with paternal age effect

Achondroplasia
Apert syndrome
Crouzon syndrome
Pfeiffer syndrome

15

Retinoblastoma
what is it?

autosomal dominant condition
causes malignant tumor of retina

16

retinoblastoma incidence

1/15,000

17

retinoblastoma gene?

RB1 gene on chromsome 13

18

Retinoblastoma gene product role?

Retinoblastoma associated protein regulates the cell cycle

19

Retinoblastoma penetrance?

90%

20

Notable clinical finding in retinoblastoma?

no reflection of red retina - looks white

21

Neurofibromatosis Type 1 (NF1)
inheritance
frequency
mutation rate

autosomal dominant
1/3000
50% new mutation

22

NF-1
expressivity?

variable

23

NF-1 Diagnostic criteria
2 or more of the following

6 or more cafe au lait
2 or more neurofibromas
1 plexiform neurofibroma
freckling in axillary or inguinal area
optic glioma
2 or more Lisch nodules
distinctive osseous lesions
affected first degree relative

24

NF1 mutation?

NF1 gene

25

NF1 gene is what?

Neurofibromin - tumor suppressor gene

26

NF1 locus

17q11.2

27

NF1 type of mutation

loss of function

28

NF1 mutation?

over 1000 mutations have been described

29

What is unique about NF1 and autosomal dominant categorization

Must have a mutation in both genes to show phenotype - but inevitably you will get a second random one

30

Tuberous Sclerosis
inheritance?
incidence
expressivity
mutation rate?
penetrance?

autosomal dominant

1/6000

variable expressivity

1/3 inherited 2/3 de novo

fully penetrant