Dominant Diseases Flashcards
IN almost all AD disoders, how will it present clinically?
significantly
are most pts with dominant inherited diseases heter or homozygous
heterozygous
homozygotes are almost always affected more ____ than heterozygotes with AD
severely
what are the 3 mechanisms for AD occur
- haploinsufficiency
- gain of function mutations
- dominant negative mutations
Define haploinsufficienty
expression from one copy of gene is not adquate to meet physiological requirements and produce a normal phenotype
Half is not enough!
mutations in haploinsufficiency always have what result
loss of function
what types of mutations can cause loss of function
almost all: missense, nonsesne, splice, framshift, deletion, insertoin, translocation
What are some examples of haploinsuficiency
TFs
prophyria’s
marfan syndrome, Type I osteogenesis imperfecta
What does NPS stand for?
Nail Patella syndrome
Where is the mutation in NPS
Lmx1b
What does LMX1B gene encode
Lmx1b transcription factor
what does Lmx1b transcription factor play a role in
dorso-ventral patterinning of limbs
what is pleitropy
clinical presentation affects a lot of seemingly unrelated organ systems
what disease has nail dysplasia, absent/hypoplastic patellae, elbow dysplasia, pterygia, extoses of the ilia, contractures and hyperextensibility of interphalgneal joints, kidney disease/failure, glaucoma
NPS
what is penetrance
probably that an individual will present with a phenotype given a certain genotype (the probability they will actually present)
What kind of penetrance does NPS have
complete - 100% will have phenotype
what is variable expressitivity
individuals carrying the same mutation may present with different phenotypes
does NPS have variable expressivity?
yes
why does variable expressivity occur
variation of other genes like modifier genes
stochastic events in development (random chance)
variable expressivity is not caused by what
allelic heterogenieity
all mutations that lead to NPS result in what
loss of function resulting in haploinsufficiency
Cleidocranial dysplasia has a mutation where?
Runx2
What is MOI for Cleidocranial dysplasia?
AD
Mutations in TF often cause a range of what
clinical features
why do mutations in TF often cause of a range of clinical features
b/c the same factor is used in different cell types at different stages in developement
how do most TF mutations act
most via haploinsuffiency
What defect is prophyrias
enzyme defects (enzymopathies of heme biosynthesis)
what is exception of enzymopathies being AR
prophyrias
acute attacks of vomiting & pain, neurological/psychiatric problems, cardiovascular symtpoms is what disease
acute hepatic porphyrias
What does AIP stand for
acute intermittent porphyrai
What is the major acute hepatic porphyria?
AIP
