Autosomal Dominant disorders Flashcards

1
Q

Mutation rate and penetrance of achondroplasia

A

80% new mutation rate

100% penetrance

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
2
Q

Clinical manifestations of achondroplasia

A
Small stature  Males 4’ 3”     Females 4’
Rhizomelic limb shortening
Short fingers
Genu varum
Trident hands
Large head/frontal bossing
Midfacial retrusion
Small Foramen Magnum/Craniocervical instability
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
3
Q

Mutation of achondroplasia is in the _____ gene which codes for ____

A

FGFR3

Fibroblast Growth Factor Receptor 3

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
4
Q

achondroplasia mutation is on chromosome ______ at nucleotide ____

A

Chromosome 4p16.3 nucleotide 1138

Glycine to arginine missense mutations

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
5
Q

Example of paternal age effect

A

Nucleotide 1138 of the FGFR3 gene has the highest new mutation rate known in man

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
6
Q

Pure dominant vs incompletely dominant

A

Pure: Homozygotes and Heterozygotes are both equally affected
Incomplete: Homozygotes are affected more severely

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
7
Q

Retinoblastoma mutation occurs at the ___ gene on chromosome ____.

A

RB1

13

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
8
Q

Diagnostic criteria for Neurofibromatosis Type 1

A
6 or more café-au-lait spots
2 or more neurofibromas 
1 plexiform neurofibroma
Freckling in the axillary or inguinal area
Optic glioma
2 or more Lisch Nodules
Distinctive osseous lesions
Affected first degree relative
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
9
Q

Mutation for Neurofibromatosis occurs at the ____ gene on chromosome ______.

A
NF1   
Neurofibromin- tumor suppressor gene
Chromosome 17q11.2
Loss of function mutation
*** Must have mutation in both genes to show phenotype
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
10
Q

Two disease we discussed that exhibit variable expressivity

A

Neurofibromatosis, Marfan’s, and Osteogenesis imperfecta type 1

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
11
Q

Clinical manifestations of osteogenesis imperfecta type 1 (4)

A

Multiple fractures
Mild short stature
Adult onset hearing loss
Blue sclera

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
12
Q

Mutation for osteogenesis imperfecta occurs on the ____ gene, encoding for ______ on chromosome _____

A

COL1A1
Collagen type 1 alpha 1
Chromosome 7q21.3

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
13
Q

Clinical manifestations in Marfan’s (4)

A

Systemic disorder of connective tissue
Ocular
Skeletal
Cardiovascular

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
14
Q

Mutation for Marfan’s occurs on the ____ gene, encoding for ______ on chromosome

A

FBN1
Fibrillin- extracellular matrix protein
Chromosome 15q21.1

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
15
Q

Mutation in the FBN1 gene is a _____ mutation that reduces the number of ____

A

Dominant negative mutation

severe reduction of microfibrils

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
16
Q

Huntington disease repeat

A

Repeat of CAG

17
Q

How does parent of origin influence Huntington’s disease?

A

Early onset – paternal

Later onset - maternal

18
Q

Mutation for Huntington’s disease occurs on the ____ gene, encoding for ______ on chromosome

A

HTT
Huntingtin
Chromosome 4p16.3
The expansion of glutamine may cause an altered structure or biochemical property of the protein

19
Q

Huntington’s repeats normal vs abnnormal

A

39: full penetrance

20
Q

Myotonic Dystrophy Type 1 repeat

A

CTG

21
Q

Clinical Manifestations of Myotonic dystrophy type 1

A
Adult onset muscular dystrophy
Progressive muscle wasting and weakness
Myotonia
Cataracts
Cardiac conduction defects
22
Q

Mutation for Myotonic dystrophy occurs on the ____ gene, encoding for ______ on chromosome

A

DMPK
Myotonic dystrophy protein kinase
Chromosome 19q13.3

23
Q

Myotonic dystrophy repeat normal vs abnormal

A

5-34 normal
34-49 premutation range
>50 full mutation with 100% penetrance

24
Q

Tuberous sclerosis gene mutation

A

TSC1 or TSC2

25
Q

Tuberous Sclerosis clinical manifestation (yeah right)

A

Angiofibromas- benign tumor on nose
Cardiac rhabodmyoma- pediatric tumor of heart
Cortical dysplasias- neurons in brain fail to migrate properly
Hypomelanotic macules- albino spots
Lymphangioleiomyomatosis- not gonna bother
Multiple retinal nodular hamartomas- non cancerous tumors
Renal angiomyolipoma
Shagreen Patch- thickened pebbly skin
Subependymal nodule
SEGA
Ungual Fibroma- lumps near nail folds