Genetic disorders I Flashcards
autosomal dominant disease display what main features?
- reduced penetrance 2. variable expressivity 3. delayed onset (possibly) 4. reduced production of protein
the gene for marfan syndrome is on which chromosome?
15
what protein is defective in marfan syndrome?
fibrillin-1
what are the main organs affected by marfan syndrome?
heart, eyes, bone
what type of mutation is involved in marfan syndrome?
missense (Cys to Gly)
what are the clinical manifestations of marfan syndrome as a result of fibrillin-1 mutations?
stiffening of aortic wall, increased TGF beta activity, inflammation and MMP upregulation, elastolysis and cell disarray
what is cystic medial degeneration?
condition caused by marfan syndrome - elastic fiber disruption by pools of blue mucinous ground substance - weakens vessel wall
what is the inheritance of marfan syndrome?
autosomal dominant
EDS types I and II are characterized by mutations linked to loci that contain which genes? what do they encode?
- COL5 2. alpha chains and type V collagen
what is the histologic appearance of EDS type I?
drop out and clumping of fibers, bear paw patterns
NF type 1 is associated with what clinical symptoms?
neurofibromas
NF type 2 is associated with what clinical symptoms?
hearing loss and bilateral acoustic neuromas
what is the penetrance of NF-1?
100%
the NF-1 gene is located on what chromosome?
17
what protein is absent in NF-1?
neurofibromin
what is the normal function of neurofibromin?
tumor suppressor gene - downregulates the function of the p21 ras oncoprotein
what are the clinical symptoms of NF1?
axillary and/or inguinal freckling, cafe au lait macules, lisch nodules, neurofibromas
the NF2 gene is located on what chromosome?
22
when do patients with NF2 mutation develop symptoms?
around age 60
what protein is defective in NF2?
merlin
how does NF2 usually present?
hearing deficits, acoustic Schwannomas
what are the features of the biphasic pattern of schwannomas?
- antoni A - more fibrosis within tumor, more cellular, more dense collagen 2. antoni B - more mixoid CT, less dense
what are verocay bodies?
palisading tumor cells with dense CT between them
