Neurogenetics / epi Flashcards
What is the induction period in dz
time from exposure to causal agent to when pathogenesis of disease begins (not sx)
In general with incidence and prevalence, which should be higher?
incidence < prevalence, if nonfatal disease
what is latent period in dz
time from exposure to causal agent to when clinical sx onset
Chromosome of William’s syndrome
Chromosome 7q11
28 yo F w/ weakness of distal hand/feet muscles, mild facial weakness, festive cataract, mild heart conduction block; hx of hypotonia; mother and brother affected
Myotonic dystrophy
What type of inheritance: equal male/female about 50% affected multiple generations (vertical) male to male transmission seen
autosomal dominant
what is haploinsufficiency
in autosomal disease when with one copy, there is not enough function for normal state
Expressivity means what in neurogenetics?
which sx are expressed in an individual patient (SCA: lots of presentations of same genetic change)
What is disease with cervical cord atrophy, limb/gait ataxia, dysarthria, distal leg weakness, sensory loss, loss of LE reflexes, upgoing toes, scoliosis as child
Inheritance?
Friedreich ataxia which is autosomal recessive but has high carrier freq of 1/85
what type of inheritance:
mutation trm of 25%
equal males/females
single generation usu affected (horizontal pattern)
Autosomal recessive
Wilson’s inheritance?
autosomal recessive
What disease with progressive neurologic decline, hypotonia –> spasticity, nystagmus and head titubation, ataxia, dystonia/athetosis, ID, VLCFA normal?
Inheritance?
Pelizaeus-Merzbacher which is X-linked recessive
What inheritance?
- mother transmits 50% of time
- Fathers transmit gene to all daughters who are carriers
- only males usually
- multiple generations
X-linked recessive
What pattern of inheritance?
- 50% transmission from mother
- 100% transmission from fathers -> daughters
- only males typically affected, but some affects on females
- males more severe or die…
X-linked dominant
Menkes inheritance
X-linked recessive
Spinal bulbar muscular atrophy inheritance? (Kennedy disease)
X-linked recessive
NAme four x-linked dominant disorders
- Aicardi
- Frg X
- Rett
- Incontinentia pigmenti
variable expression due to heteroplasmy in what conditions?
WHat is heteroplasmy?
heteroplasmy is % of abnl mitochondria per cell and varies in mito disease over lifetime and by tissue
Whats the methylation deal with imprinting?
-in Angelman and Prader Willi?
only maternal is methylated, and allows for only 1/2 gene to be expressed (either from mother or father)
in Angelman: maternal deletion of 15q11-13
in Prader Willi: paternal deletion of 15q11-13
WHat is uniparental disomy?
acts like a deletion, in which two methylated (two maternal) or two unmethylated copies (two paternal) are inherited
Triplet repeat of Huntington?
CAG: hunters: catch animal game
Three categories of disease in channelopathies
- epilepsy/migraine
- neuromuscular disorders
- episodic ataxia (K/Ca) and hyperexplexia (glycine)
Diseases caused by voltage gated channel mutations (4)
- idiopathic generalized epilepsy
- Spinocerebellar ataxia type 6
- familial hemiplegic migraine
- episodic ataxia type 2
SOD1 gene
what chromosome, what dz
Chr 21, autosomal dominant ALS
calpain 3 gene
limb girdle muscular dystrophy 2A
transthyretin
peripheral neuropathy in familial amyloid polyneuropathy
MPZ gene (3)
CMT 1B: demyelinating / axonal (AD)
Dejerine Sottas
CMT2 axonal
*Infantile demylenating, adult axonal
arylsulfatase A or prosaposin
metachromatic leukodystrophy
Lesch Nyhan inheritance
x-linked
def of sterol 27-hydroxylase
cerebrotendinous xanthomatosis
globoid cell leukodystrophy
krabbe
GALC gene / galactocerebrosidase
globoid / Krabbe
aspartoacylase def; accum of NAA in brain
Canavan *inherited infantile leukodystrophy
galactosylsulfatide build up / excretion in urine in what dz
metachromatic leukodystrophy due to arylsulfatase A def
Proteolipid protein gene alteration
-dz and inheritance
PLP: Pelizaeus Merzbacher disease, X-linked dysmyelinating
GAA repeats 200-900
Freidreich ataxia chr 9, AR
gene for ataxia telangiectasia
inheritance
ATM chr 11, AR
spinocerebellar ataxia type with benign course
6
CAG repeats
spinocerebellar ataxias and DRPLA
AND Huntingtons
and spinal bulbar muscular atrophy
exception to CAG for spinocerebellar ataxia repeat is what repeat in what time of SCA?
SCA 8 has CTG repeat
CTG repeats in what? (2)
SCA type 8
Myotonic dystrophy
myotonic dystrophy what genetics / chromosome
CTG repeat, chr 19
atrophin on chr 12
DRPLA in coding region of huntingtin
ataxin 3 dz and chr?
SCA type 3: machado joseph
Chr 14
emery dreifuss muscular dystrophy inheritance
may be x linked
Fabry inheritance
x linked recessive
COL4A1
autosomal dominant small vessel disease w/ hemorrhagic stroke
Mutation in asians for SJS with CBZ
HLA-B-1502
type of SCA with pigmentary retinopathy
type of SCA w/ spasticity
7: pigmentary retinopathy
3: spasticity
SCA’s with possible seizures
SCA 10, 17, DRPLA
SCA with myokemia
5
type of episodic ataxia with really long attacks
EA 7
atlastin gene mutation / SPG4/SPAST
hereditary spastic paraplegia
nutritional mimic of HSP hereditary spastic paraplegia
copper def
