Autosomal Dominant Flashcards
Osteogenesis Imperfecta Type 1 - Associated gene
COL1A1 (collagen type 1 alpha 1)
chromosome 17
Osteogenesis Imperfecta Type 1 - Mechanism
decrease production of Pro-alpha 1 chains –>
decrease in type 1 collagen
variable expressivity
Osteogenesis Imperfecta Type 1 - Clinical presentaiton
brittle bones fractures blue sclerae (whites of eyes) normal stature adult onset hearing loss
Achondroplasia - Associated gene
FGFR3 (fibroblast growth factor receptor 3)
Achondroplasia - Inheritance
autosomal dominant
incomplete dominance
Achondroplasia - Mechanism
gain of function: Gly380Arg mutation
Receptor normally inhibits bone growth - defective receptor is always on, causing shortening of limbs
De novo: father’s germline (with age)
Homozygous state is lethal - incomplete dominance
Achondroplasia - Clinical presentation
short stature
rhizomelic limb shortening (proximal limb shorter than distal limbs)
large head with frontal bossing
short fingers, trident hands
small foramen magnum, craniocervical instability
genu varum (bow legged)
midfacial retusion (sunken in)
Neurofibromatosis Type 1 - Associated gene
NF1 gene (codes for neurofibroma-tumor suppressor gene) chromosome 17
Neurofibromatosis Type 1 - Inheritance
autosomal dominant
50% new mutation rate
Neurofibromatosis Type 1 - Mechanism
loss of function of NF1 gene
dominant but must have mutation in both genes to show phenotype - cells must develop a second mutation to cause disease
100% penetrance, variable expressivity
Neurofibromatosis Type 1 - Clinical presentation
must have 2 of the phenotypes Cafe au Lait spots axillary and inguinal freckling multiple neurofibromas lisch nodules (spots/bumps on eye)
Marfan Syndrome - Associated gene
FBN1 (fibrillin-extracellular matrix)
chromosome 15
Marfan Syndrome - Mechanism
decrease in microfibrils
variable expressivity
Marfan Syndrome - Clinical presentation
connective tissue disorder ocular, skeletal, and cardiovascular manifestations enlarged aortic root appear tall and skinny (long-limbed) hypermobile joint pectus excatum/carnatum
AD Polycystic Kidney Disease - Associated gene
ADPKD
Chromosome 16
OR
ADPKD-1
Chromosome 4
AD Polycystic Kidney Disease - Mechanism
locus heterogeneity
AD Polycystic Kidney Disease - Clinical presentation
enlarged kidneys with multiple cysts
end stage renal disease
extra renal cysts (i.e. in pancreas)
intracranial aneurysms
Familial hypercholesterolemia - Mechanism
mutations in gene encoding LDL receptor (can’t clear LDL from blood stream)
Familial hypercholesterolemia - Clinical presentation
high cholesterol levels
deposition of cholesterol throughout body
premature coronary artery disease
Retinoblastoma - Associated gene
RB1 gene - regulates cell cycle
Chromosome 13
Retinoblastoma - Clinical presentation
malignant tumor of retina
Tuberous Sclerosis - Associated gene
TSC1 or TSC2
(mutation in either)
regulates cell growth, proliferation
encodes hamartin and tuberin proteins
Tuberous Sclerosis - Mechanism
fully penetrant
locus heterogeneity
Tuberous Sclerosis - Clinical presentation
must have 2 major of 1 major minimum Skin (patches, growths) cysts on kidneys cardiac rhabdomyoma in infants seizures psychiatric disorders
