Autosomal Dominant Disorders Flashcards Preview

Foundations 1 > Autosomal Dominant Disorders > Flashcards

Flashcards in Autosomal Dominant Disorders Deck (10):

types of dominant mutations

loss of function through haploinsufficiency or dominant negative mutations

gain of function



the level of product required for normal function might be so critical that the amount produced by a single functioning allele would be inadequate

ex. familial hypercholesterolemia - lack of LDL receptors


dominant negative effects

the abnormal protein interferes or competes with the normal function of the normal protein

ex. insulin Chicago - phenylalanine to leucine substitution causes mutant insulin to lose function but also bind to receptors and prevent regular insulin from binding, leads to hyperinsulinemic diabetes


five mutations that leads to familial hypercholesterolemia

gene deletion or decreased synthesis

impaired transport to Golgi

mutant receptors fail to bind LDL

failure of receptors to cluster in coated pits

impaiment of receptor recycling


types of dimer mutations that lead to dominant negative effects

mutation in one allele interferes with dimer association and interaction with other molecules

mutation where one allele increases affinity but results in decreased interaction with other molecules (>75% loss of function )

mutation in one allele results in 75% reduction in function by interfering with interaction with other molecules, despite that dimer association is normal


osteogenesis imperfecta

protein suicide - abnormality in either the pro-alpha1 or pro-alpha2 genes leads to improper formation or stability of the collagen, leading to rapid degradation in 3/4 different fiber compositions

phenomenon called protein suicide, leads to many bone deformities and weakenss


Classical Ehlers-Danlos Syndrome

defect in alpha-1 and 2 of type 5 collagen

some symptoms include delayed motor milestones, sofy and velvety skin that bruises easily, creates cigarette paper scars, hyperelastic and fragile

fleshy lesions, joint hypermobility, mitral valve prolapse, hiatial hernia, anal prolapse, pes planus (flat feet)



characterized by small stature, disproportionate shortening of the proximal limb segments, short base of the skull with a large head, spinal stenosis, normal intelligence

caused by a single base substitution that results in a glycine to arginine mutation at position 380 of the gene product of the fibroblast growth factor receptor 3 (FGFR3), which constitutively represses chondrocyte proliferation

gain of function mutation


Wolf-Hirschhorn Syndrome (4p-)

deletion of terminal 4p, which inc ludes FGFR3, frowth deficiency, microcephaly, severe mental deficiency, hypertelorism, (widely spaced eyes), cleft lip and/or palate, micrognathia (small mandible)

haploinsufficiency, different from achondroplasia


familial male precocious puberty

sex-limited trait, causes early signs of puberty in males

due to mutation that leads to constitutive activation of the leuteinizing hormone receptor, which leads to increased testosterone production

gain of function mutation that leads to