Gain of Function Mutation Flashcards
What is a gain of function mutation
increased or novel gene function
What type of mutation causes gain of function
missense, gene duplciations, chromosomal translocations
What is main disease when FGFR3 is mutated
achondroplasia
What does FGFR3 encode?
tyrosine kinase receptor
What does TD stand for
Thanatophoric Dysplasia
What is mode of inheritance of TD
AD
Do pts with TD usually survive?
usually still born
what mutation is thanatophoric dysplasia caused by
sporadic mutatins
Death in uterio or perinatal lethal, limb shortening, severe frontal bossing, very small chest, death due to respiratory failure is what disease
Thanatophoric Dysplasia
What is the main type of Thanatorphic Dysplasia
TD1
What is the most common form of swarfism
Achondroplasia
What are most mutations caused by that cause achondroplasia
sporadic mutation
What is the specific mutation that causes achondroplasia
G380R
If pt has short stature, shortening of long bones of limbs, large head, low nasal bridge, lumbar lordosis, normal life expectancy & intelligence is what disease?
achondroplasia
What is a major life threatening complication that can occur with pts in achondroplasia
compression of foramen magnum
When does homozygous achondroplasia occur
when two people with achondroplasia mate
what is the phenotype of homozygous achondroplasia
perinatal lethal (comparable to TD1)
What test could be done to confirm if pt has homozygous achondroplasia and TD1?
Look at parents - if both parents have achondroplasia then pts is homozygous achondroplasia
What is the biggest role in FGFR3 regarding development
bone growth
What is biggest role in FGFR2 regarding development
skull
What is disease when FGFR2 is mutated?
Apert syndrome
gain of function and loss of function mutations will have what kind of phenotypes compared to each other
opposite
WHat is FGFR3’s role in chondrocyte proliferation
it stops proliferation so it slows bone growth
Gain of function mutations do what to dimerization of RTKs
they increase dimerization
A loss of function mutation has what kind of phenotype compared to achondroplasia
opposite
Explain the knockout of FGFR3 and knock in of FGFR3
knockout: longer growth of limbs
knock in: shorter limbs, smaller skeletons
What does CATSHLS stand for
camptodactylyl tall stature, and hearing loss syndrome
what human disease has loss of function in FGFR3?
CATSHLS
clinical presentatuion: tall stature, severe lateral tibial deviation, scoliosis, compacdyctyal is what disease
CATSHLS
What does FOP stand for
fibrodysplasia ossificans progressiva
FOP is caused by mutations in what gene
ACVR1
What is ACVR1?
BMP receptor part of TGF beta family
clinical presentation: heterotropic ossification of skeletal muscles, tendons, ligaments and fascia, congenital malformation of big toes is what disase
FOP
clinical presentation: heterotropic ossification of skeletal muscles, tendons, ligaments and fascia, congenital malformation of big toes is what disase
FOP
What kind of mutation is in ACVR1?
gain of function
What does BMP stand for?
Bone Morphogenetic proetins
What do BMPs do?
induce bone and cartilage formation
Gain of function mutations in BMP receptor leads to what
heterotrophic ossification
What is the BMP receptor
ACVR1
