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36 Cards in this Set
- Front
- Back
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SMA |
autosomal recessive deletion of "survival of motor neuron" gene (SMN1) on chr 5q |
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familial ALS genes
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SOD1 --> 20%
TARDBP gene --> TDP-43 protein (transactive response DNA-bonding protein 43) --> 5% familial but also sporadic FUS gene mutations (fused in sarcoma protein) --> 5% C9orf72 (chromosome 9 open reading frame 72) --> 30% |
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myelin associated proteins
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MPZ (myelin protein zero) --> PNS
myelin-associated glycoprotein --> CNS and PNS PMP22 (peripheral myelin protein 22) --> PNS MOG (myelin-olygodendrocyte glycoprotein) --> CNS OMgp (oligodendrocyte-myelin glycoprotein) --> CNS |
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CMT genetics
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CMT1A --> AD; PMP22 duplication on chr 17; 50-60% of molecular CMT cases;
CMT1X --> X-linked; GJ1B gene, connexin 32 protein; 15-20% of molecular CMT cases CMT1B --> AD; MPZ duplication on chr 1; 5-15% of molecular CMT cases CMT2A --> AD; MFN2 gene; 5% molecular CMT cases and 20% CMT2 cases many other known mutations and genetic defects |
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HNPP genetics
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autosomal dominant
deletion of PMP22 on chr 17 in ~75% |
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FSHD genetics
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autosomal dominant decrease in D4Z4 repeats in chr 4
up to 30% of cases are sporadic |
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genetics of dystrophinopathies
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x-linked recessive
mutation of DMD (dystrophin) gene on Xp21 duchenne --> no dystrophyn at all becker's --> some dystrophin present, disease is milder and later onset |
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X-linked myopathies
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dystrophinopathies (DMD and BMD)
myotonic dystrophy Emery-Dreifuss |
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DM1 genetics
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mutation in DMPK gene on chromosome 19 results in CTG trinucleotide repeat
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DM2 genetics |
mutation in ZNF9 gene (zinc finger protein 9) in chr 3 results in CCTG repeat
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mutations associated with familial AD |
PSEN1 on chr 14 --> most common; early onset; increased ratio of Abeta 42; may have myoclonus, gait and pseudobulbar
APP on chr 21 --> second most common cause of familial AD; usually increase rate/production of APP PSEN2 on chr 1 --> rarest familial AD; may also have seizures |
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ApoE gene location
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APOE gene is on chr 17
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risk of AD in ApoE E4 carriers |
ApoE E4 allele confers odds ratio x4 for carriers and x15 for homozygous of developing late-onset AD
50% lifetime risk of developing AD by age 80 if 1 copy highly likely AD by age 80 if two copies |
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tau gene
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microtubule-associated protein MAPT on chr 17
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TARDBP gene |
TAR DNA binding protein gene
encodes TDP-43 associated with FTLD-TDP proteinopathies on chr 1 |
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mutations associated with FTLD
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microtubule-associated protein MAPT on chr 17 --> hyperphosphorilated tau deposition
progranulin gene GRN on chr 17 --> TDP-43 deposition C9ORF72 gene on chr 9 --> TDP-43 deposition |
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genetic mutations associated with deposition of TDP-43
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TARDBP gene mutations on chr 1
progranulin gene mutations (GRN) on chr 17 C9ORF72 mutations in chr 9 |
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low grade astrocytoma genes
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TP53 mutation
Isocitrate dehydrogenase mutation (IDH1) better prognosis |
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glioblastoma genes
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EGFR amplification
PTEN alteration (chromosome 10q loss) |
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oligodendroglioma mutation
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1p and 19q codeletion - better prognosis
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medulloblastoma mutation |
Isochromosome 17q
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schwanoma mutations |
Loss of 22q, mutations of the NF2 gene
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genetic tumor syndromes |
NF1 --> chr 17 --> plexiform neuroma, optic gliomas
NF2 --> chr 22 --> Vestibular and PN shwannoma, meningioma tuberous sclerosis --> chr TSC1/9q, TSC2/16p --> SEGA VHL --> chr 3p --> Hemangioblastoma |
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mTOR
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mammalian Target Of Rapamycin protein
Overactivatin of mTOR signaling (caused by mutations of TSC1 and TSC2 and other regulatory proteins) leads to cortical malformations, including tubers, focal cortical dysplasia type IIb, ganglioglioma, and hemimegalencephaly |
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PARK1 and 4
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SNCA gene on chr 4q (PARK1/PARK4 loci)
PARK 1 --> AD and sporadic PD, prominent dementia PARK 4 --> AD and sporadic PD, overexpression of SNCA, varying phenotype |
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PARK8
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LRRK2 gene on chr 12q --> leucine-rich repeat kinase
most common familial PD AD with incomplete penetrance LRRK2 --> dardarin protein --> involved in phosphorylation of alpha-synuclein and tau, among others |
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PARK2
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parkin gene --> chr 6q
E3 ubiquitin ligase --> involved in ubiquination of proteins and vesicular transport selective nigrostriatal degeneration without Lewy body formation |
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PARK5
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UCHL1 gene --> 4q --> ubiquitin carboxy-terminal hydrolase
AD PD |
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PD genetics
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15% have first-degree relative with PD
5% of patients have mutations in specific genes --> PARK 1 and 4 --> SNCA gene PARK2 --> parkin gene on chr 6 --> E3 ubiquitin ligase (no Lewy bodies) PARK8 --> leucine-rich repeat kinase --> dardarin protein (most common) PARK5 --> UCHL1 gene --> 4q --> ubiquitin carboxy-terminal hydrolase PARK6 --> PINK1 --> mitochondrial kinase PARK7 --> DJ-1 |
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PD genetic mecanisms
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overproduction or malfunction of alpha-synuclein --> PARK 1 and 4 --> SNCA gene chr4
defective ubiquitin pathway --> PARK 2 and 5 --> parkin and UCHL1 genes mitochondrial dysfunction --> PARK6 --> PINK1 protects mitochondria from parkin-induced autopahy oxidative stress --> PARK7 --> DJ-1 protects against oxidative stress |
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PD mechanisms --> overproduction or malfunction of alpha-synuclein
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PARK 1 and 4 --> SNCA gene chr4
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PD mechanisms --> defective ubiquitin pathway |
PARK 2 and 5 --> parkin and UCHL1 genes
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PD mechanisms --> mitochondrial dysfunction |
PARK6 --> PINK1 protects mitochondria from parkin-induced autopahy
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PD mechanisms --> oxidative stress |
PARK7 --> DJ-1 protects against oxidative stress
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myoclonus-dystonia genetics |
autosomal dominant with complete paternal penetrance and 15% maternal penetrance
DYT11 --> chr 7; SGCE gene DYT15 --> chr 18; unknown gene |
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genetics of Friedreich ataxia
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autosomal recessive GAA repeat expansion in an intron of the frataxin (FXN) gene |
