Autosomal Dominant Inheritance Flashcards
mutations in one allele that can lead to structural change in protein that interferes with the function of the wild-type protein
dominant negative mutations
example of a dominant negative mutation that has a mutation in collagen 1 alpa1 chain and has sx’s of BITE
osteogenesis imperfecta
this is due to loss of function of fibrillin-1 (FBN1), making it unable to sequester TGF-beta
Marfan syndrome; dominant negative mutation
in autosomal dominant inheritance, what is the chance of a child inheriting disorder
50%
examples of incomplete dominance (2)
familial hypercholesterolemia
achondroplasia
example of autosomal dominant mutation that leads to gain of function and TF sequestration
Huntington’s disease
phenotypically normal family members do or do not transmit phenotype to children
do not transmit
most common cause of dwarfism
achondroplasia
rhizomelic shortening of arms and legs, macrocephaly and prominent forehead
achondroplasia
caused by FGFR3 mutations
achondroplasia
gain of function mutation that results in constitutive activation of FGFR3 and inhibition of chondrocyte proliferation
achondroplasia
unaffected parents with affected child of achondroplasia would deal with what
gonadal mosaicism
80% de novo mutations in paternal germline
achondroplasia
caused by mutation in NF2 tumor suppressor gene
Neurofibromatosis 2
bilateral vestibular schwannomas (benign tumors of nerve VIII) and meningiomas
neurofibromatosis 2
patient presents with tinnitus, sensorineural hearing loss, and balance problems (think damage to CN VIII)
neurofibromatosis 2
mutation in one allele is inherited, then a second mutation occurs in one cell that can lead to what
a tumor
the two-hit hypothesis that leads to a tumor manifests as what kind of cancer
autosomal dominant
deals with variable expressivity and locus heterogeneity at PKD1 and PKD2 loci
autosomal dominant polycystic kidney disease (ADPKD)
one normal and one abnormal allele at particular locus, the loss of normal allele produces a locus with no normal function
loss of heterozygosity
presentations of this disease include: progressive renal failure*
renal and hepatic cysts*
UTIs
hematuria
nocturia
flank pain
hypertension
end-stage renal disease by 60***
autosomal dominant polycystic kidney disease (ADPKD)
caused by mutation in APC gene
(de novo gene mutations); autosomal dominant
familial adenomatous polyposis
present in affected individual but absent from both biological parents’ genomes
de novo mutation
leads to buildup of adenomatous polyps in colon; almost 100% form colonic tumors by 40 years (many poly[s unlike Lynch Syndrome)
familial adenomatous polyposis
