Genetics

Question 1

Huntington’s

Answer 1

amplification of CAG triplet repeat (in exons), chromosome 4p16.3, from father
normal 9-37, full mutation 39-91
symptoms: core, dementia, rigidity
polyglutamine, low BDNF in cerebellum, cortex, and striatum
inability to degrade HTT, mHTT via C 2/3

Question 2

Fragile X

Answer 2

amplification of CGG triplet repeat (in promotor region), chromosome Xq27.3 or Xq28, from mother
normal 5-40, full mutation >200
presents with: (M) large testes (F) FXTAS
protein: FMRP (abundant in brain and testes), transports mRNAs from nucleus, interferes with DNA transcription

Question 3

Neurofibromatosis 1

Answer 3

single gene NF1 - neurofibromin, 1:4500, autosomal dominant, 
function - negative regulator of RAS, tumor suppressor 
presents: cafe-au-lair spots, freckling, peripheral neurofibromas, lisch nodules

Question 4

Lesch-Nyhan

Answer 4

single gene- HPRT, X-linked (more common in males)
presents: hyperuricemia, gout, spasticity of legs, self-mutilation, urate crystals in diapers
inability to salvage hypoxanthine and guanine from degradation pathways

Question 5

Hurler

Answer 5

lysosome storage MPS 1, autosomal recessive
a-L-iduronidase
accumulation: heparan sulfate, dermatan sulfate
presents: gargoylism (course facies), corneal clouding, short
death by age 10

Question 6

Hunter

Answer 6

lysosome storage MPS 2, x-linked recessive
iduronate sulfatase
accumulation: heparan sulfate, dermatan sulfate
presents: brachycephaly, clubbing of fingers, hepatosplenomegaly, puffy face. left inguinal hernia
death by age 15

Question 7

Sanfilippo

Answer 7

lysosome storage MPS 3
four types
accumulation: heparan sulfate
presents: sever CNS degeneration w/ progressive neurological disease

Question 8

Neurofibromatosis 2

Answer 8

single gene NF2 - merlin, 1:210,000, autosomal dominant
function - tumor suppressant 
presents: vestibular schwannomas, hearing loss

Question 9

Tay-Sachs

Answer 9

sphingolipid breakdown
hexosaminidase A
GM2 accumulation in CNS/ANS, retina - cherry red spot
presents: blindness, inability to swallow
death by age 2-3

Question 10

Sandhoff

Answer 10

sphingolipid breakdown
hexosaminidase B
GM2 accumulation in CNS/ANS, retina - cherry red spot
presents: blindness, inability to swallow
death by age 2-3

Question 11

Krabbe

Answer 11

galactocerebrosidase

Question 12

Fabry

Answer 12

a-galactosidase
Cer-Glc-Gal –> Cer-Glc
angiokeratomas

Question 13

Gaucher

Answer 13

b-glucocerbrosidase
onion looking cells
Cer-Glc –> Ceramide

Question 14

Niemann-Pick

Answer 14

sphingomyelinase

Question 15

Alzheimers

Answer 15

dementia, amyloid plaques

causes: most unknown, some early and late familial onset

Question 16

early onset familial AD

Answer 16

PSEN1 APP PSEN2 mutations

Question 17

late onset familial AD

Answer 17

APOE - regulates amyloid level in brain
e4>e3 - Ab aggregation, neurofibrillary tangles, neural toxicity
e3>e4 - synaptic repair, Ab clearance