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Flashcards in CSIM inherited diease Deck (68):

in x linked inheritance what is the chance of having a child with the mutation? and what is the chance of having a child with the disease?

1/4- girls cant get x- linked disease


define penetrance

what proportion of individuals with a gene mutation with manifest disease


define expression

how does the disease express itself- you can get different clinical features from the same mutation in the same gene


etymology of the word pedigree?

goose feet- thats what the family tree looks like


how to denote consanguineous relationship in genetics?

double line


define polymorphism

presence of genetic variation in the population e.g. different recipes for the same things


what pattern of inheritance do most breast cancers follow?

autosomal recessive


what is the two hit theory?

you are likely to at some point in your life develop a mutation in one allele (hit 2)
if you start off with one already (hit 1 ) then you are much more likely to develop cancer


what is 'loss of hetrozygosity'

normally you are heterozygous
if you have a mutation in one allele then you are still heterozygous
if you get a mutation in the other one as well then the alleles are the same so you are now homozygous


how do BRCA 1 and 2 cause cancer?

mutation - > produce tumour suppressor proteins


what cancers do BRAC1 and 2 mutations cause?

ovarian and breast (amongst others)


what difference is there in the screening of breast cancer in younger and older women with a BRCA mutation and why?

younger woman
- avoid x-ray due to increase risk of GIVING them breast cancer
- breast tissue is denser so x-ray not as good
-use MRI or US instead


an isolated abnormality is normally... and more rarely due to?

a single gene defect


3 causes of syndromic abnormalities?

maternal exposure e.g. sodium valporate syndrome
single gene defect


define dysmorphic features

minor changes in features that are not common in the population


define aneuploidy

abnormal number of chromosomes


what are the only 3 viable trisomies and which chromosomes?

edward's- 18
down's- 21
patau's- 13


chromosomal abnormality in Turner's syndrome?

1 x
only viable monochromy


what immediate investigation can be dome in suspected developmental abnormality in the neonates?

rapid (in 48 hrs) screen for trisomies and for sex chromosome abnormalities by PCR


define de novo

mutation in a gene / chromosome that is present for the first time in a family


what is FISH and when is it used?

Fluorescent In Situ Hybridisation
Used to detects submicroscopic deletions
Used to detect chromosome rearrangements


what can chromosomal microarrray NOT detect? which test can do this?

single nucleotide variants
clinical exome sequencing


what will the chromosomal array in a normal male say?

arr(1-22)x2 XYx1


which test can look for balanced chromosome rearrangement?



who cant a male pass on an x linked disease to and why?

they get their x chromosome form their mother


how can women who carry x linked abnormalities have symptoms of that disease?

genomic imprinting: x chromosome deactivation randomly affects their normal x so the faulty one proliferates?


2 most important bits of information following a seizure?

collateral hx
capillary blood glucose - DEFG


symptoms of delirium tremens?



most appropriate treatment for delirium tremens with seizures? what do you need to consider in ALD?

chlordiazepoxide (in the benzo class)
reduced dose due to hepatoxicity


what effect does phenytoin have on metabolism?

enzyme inducer


how long after the start of a seizure should you treat it?and what drug / route?

5 mins- this is status epilpticus and is a medical emergency

first line in IV lorazepam
if no access do PR diazepam (IV can cause thrombophlebitis)
people can carry buccal midazolam

then give phenytoin sodium - monitor ECG due to bradycardia


best drug for treating partial / focal seizures

carbamazepine (can use lamotrigine)


why do you need to be careful when using carbamazepine and warfarin?

carbamazepine is an INDUCER so will reduce the conc. of warfarin- MONITOR


what happens to GGT when using carbamazepine?

increases due to enzyme INDUCTION


what gene is TP53 related to?

early onset breast cancer


why wouldnt you offer breast screening to a man with the BRCA mutation?

raised risk but still not that high


when would breast screening be offered in a girl found to have the BRCA 1 mutation?

MRIs from 30
Mammography from 40


which BRCA gene carries the higher life time risk of breast cancer?

1 >2


in autosomal recessive disease: if your parents are healthy but your sibling has the disease what is the chance youre a carrier?



why was the incidence of leukaemia in Hiroshima highest about 10 years after the event?

cancer requires a single cell to undergo a series of multiple mutations, not just one


what in the normal function of an oncogene?

promotes cell growth / division


% of cancers that are inherited?

5% (another 10% seem to be familial but NOT inherited)


how p53 supposed to work?

tumour suppressor protein that should arrest the cell cycle at G1 if there is damage to the DNA


which gene is associated with Li Fraumeni syndrome? and what is that?


inherited gene defect that pre disposes you to cancer


BRCA1 and 2 follows what form of inheritance?

autosomal dominant


women between 30 and 60 with the BRCA 1 mutation are offered what screening?

yearly MRIs between 30 and 40 then MRI plus mammogram until 60


what is lynch syndrome and what is the mechanism?

AKA hereditary non-polyposis colorectal cancer, its an inherited cancer predisposition syndrome

germline mutations in mis-match repair genes increases risk of lots of cancers (most common are colorectal, endometrial, stomach, ovarian)


red flags for lynch syndrome?

- known LS causing mutation in the family
- three or more relatives with a LS associated cancer AND
- one is a 1st degree of the other two
- two successive generations affected (therefore dominant
- at least one before 50


what is responsible for 'familial' cancer?

there are lots of low penetrance / low risk alleles
environmental factors


define heterozygote and homozygote

heterozygote- having two different alleles for a particular gene
homozygote - having identical alleles for a particular trait


define anticipation

as a disorder is passed on to the next generation symptoms present earlier with each generation


what kind of Alheimerzs has a strong familial inheritance?

early onset (<55)


what 3 main body systems are affected in Marfan's syndrome?

heart - valve problems, dissestions
eyes - lens dislocations
skeletal feature- long fingers, scoliosis etc.


what should be monitored in marfan's?

frequent echos to check root size
(also eye exams)
due to risk of aortic dissection


how can a child with a dominant genetic disorder be the first in the family to have it? (5)

- de novo - first time the gene has mutated
- there is incomplete penetrance so in earlier generations it was not picked up (subtle phenotype in parents or not at all)
- could be x linked inheritance: if the mother had it she would pass on the Y to her son
- mosaicism
- imprinting


what is an imprinted disorder?

certain genes are expressed depending on which parent you inherit them from.

the allele from the MOTHER is imprinted ('silenced')
the allele fro the father is active


what is mosaicism?

if in development a clone of your cells gets mutated you could end up with only a proportion of your cells having a defect. if this effects , say, a some of a woman's oocytes she could pass on a defect to her child


in x linked inheritance what are the probabilities of a carrier female having:
1. a normal male
2. an affected male
3. a normal daughter
4. a carrier daughter

all 1/4


X linked : what is the probability an affected male will pass on the condition to their son?

the son gets the X chromosome from their mother


X linked: what is the probability that an affected male will pass on the defect to their daughter?



what is the role XIST on the X chromosome?

IXST is a gene that produces a functional RNA that coats the rest of the X chromosome thereby inactivating it.

if IXST is methylated then it is INACTIVATED and therefore it cannot coat the chromosome so that chromosome is ACTIVE


if you have two X chromosomes how is one of them chosen?

one is RANDOMLY deactivated by the XIST gene


which part of the X chromosome behaves like an autosome?

the pseudo autosomal regions 1 and 2 (PARS 1 and PARS2)
both copies of these regions will be active


if a female is a carrier of an X linked condition, why might she express some features of that condition?

in each cell the inactivation of some of the X chromosomes is completely random. so there will be some normal and some defected cells in everyone.
if the defect is one that promotes cell proliferation then there will be more of these defected cells than normal ones
this means females can be an effected true carrier, have a severe phenotype and be everything in between


how is duchenne's muscular dystrophy passed on?

x linked


what is a paraganglioma?

tumour of the sympathetic ganglia
commonly arise in the head and neck


paragangliomatosis: if you inherit the faulty SDHA gene from your dad, will you have the disease and why?


this is an example of genomic imprinting
imprinted genes are un-silenced when inherited from your dad (NOT methylated)


what does micro satellite instability tell you about colon cancer?

a low MSI means it's probably a sporadic cancer rather than genetic
if its high its more likely inherited