Autosomal Dominant Diseases Flashcards
*Achondroplasia complete? or incomplete penetrance?
complete penetrance
Achondroplasia clinical
autosomal dominant small stature Rhizomelic limb shortenieng short fingers genu varum trident hands large head, frontal bossing midfacial retrusion small foramen magnum/ craniocervical instability
Achondroplasia molecular
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
Achondroplasia pure or imcompletely dominant?
Imcompletely dominant
-homozygotes affected more than heterozygote
*neurofibromatosis type 1 and osteogenesis impoerfecta type 1 are example of
variable expressivity
Neurofibromatosis type 1 clinical
- 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
Neurofibromatosis type 1 molecular
- 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
Osteogenesis Imperfecta Type 1
- Autosomal Dominant
- 1/30000-50000
Osteogenesis Imperfecta clinical
multiple fractures
mild short stature
adult onset hearing loss
blue sclera
Osteogensis imperfecta mutation
- mutation COL1A1
- collagen type 1 alpha 1 mut
- Chr 7q21.3
- decreased pro-alpha 1 chain——-> reduce the type 1 collagen by half
Marfan Syndrome
Autosomal dominant
1/5000
25% new mutation rate
Marfan syndrome clinical
- systemic connective tissue disorder
- ocular disorder
- skeletal disorder
- cardiovascular disorder
Marfan syndrome mutation
- FBN1
- reduction in microfibrills
- Chr 15q21.1
- Autosomal Dominant Polycystic Kidney Disease info
1/1000 births
5% new mutation rate
Autosomal dominant polycystic kidney disease clinical
- bilateral renal cysts
- cysts in other organs
- vascular abnormalities
- end stage renal disease in 50% by 60yrs old
Autosomal dominant polycystic kidney disease mutation
PKD1 chr 16p13.3
PKD2 chr 4q22.1 (15%)
Polycystin 1 and 2
truncated protein
*Familial Hypercholesterolemia info
Autosomal dominant
1/200-500
very low new mutation
familial hypercholesterolemia clinical
- high cholesterol (>310)
- high LDL (>190)
- Xanthomas (cholesterol under skin)
- premature coronary artery disease
familial hypercholesterolemia molecular
mutation
LDLK
APO8
PCSK9
Huntington Disease info
Autosomal dominant
CAG repeat
1/10000
paternal anticipation
Huntington Disease clinical
- progressive neuronal degeneration
- motor, cognitive, psychiatric disturbances
- onset 35-44 yrs old
- death 15 yrs after onset
Huntington Disease molecular
mutation HTT
Chr 4p16.3
expansion of glutamine
Myotonic Dystrophy Type 1
Autosomal dominant CTG repeat (5-34 normal) (34-49 premutation) (>50 100% penetrance) 1/20000 maternal anticipation
Myotonic dystrophy type 1 clinical
adult onset muscular dystrophy progressive muscle wasting myotonia (cannot release grip) cataracts aortic coarctation
Myotonic dystrophy type 1 molecular
- mutation DMPK
- myotonic dystrophy protein kinase
- Chr 19q13.3
- important for muscle, heart, brain cells
