Inheritance and testing in genetic disease Flashcards Preview

Physiology > Inheritance and testing in genetic disease > Flashcards

Flashcards in Inheritance and testing in genetic disease Deck (40)
Loading flashcards...
1
Q

why are models of disease inheritance important?

A

to know how genetic disease are inherited to allow appropriate medical advice to be given
predict risk of being affected by disease for family members of an affected individual - screening and treatment
predict risk of being carriers of disease for family members of an affect individual - risk to unborn child, reproduction choices

2
Q

autosomal dominant inheritance

A
50% risk to offspring
transmission by males and females
males and females equally affected
affected individuals should have an affected parent 
tends to occur in every generation
3
Q

huntington disease

A

incidence = 1/10,000
onset 35-55 years of age
affects movement, cognitive and psychiatric behaviours

4
Q

autosomal recessive inheritance

A

25% risk to offspring - with 2 carrier parents
males and females equally affected
usually no previous family history
most commonly affects siblings

5
Q

cystic fibrosis

A

commonest autosomal recessive disease affecting caucasians
incidence = 1/2,500 - 250 babies a year
carrier frequency = 1/25
mutation of the CF transmembrane conductance regulator (CFTR)
main defects in the lungs and pancreas caused by thickened mucus

6
Q

example of autosomal dominant disease

A

huntington disease

7
Q

example of autosomal recessive disease

A

cystic fibrosis

8
Q

x-linked recessive inheritance

A

no male-to-male transmission
males affected almost exclusively
transmitted through unaffected female carriers

9
Q

examples of x recessive linked inherited conditions

A

haemophilia A and B

Duchenne muscular dystrophy

10
Q

x linked dominant inheritance

A

males and females affected - often more females
females less severely affected
affected males can transmit to all daughters but none of their sons
affected females transmit to 50% of her offspring
very rare
males usually more severely affected than females due to rescuing affect by second x chromosome

11
Q

examples of x-linked dominant inheritance

A

rett syndrome, incontinentia pigmenti, fragile X syndrome

12
Q

x-linked dominant inheritance with male lethality

A

male is so severely affected that survival is unusual

live born males with these conditions often have an additional x chromosome

13
Q

x-linked dominant with male sparing

A

only females affected but mechanism unclear

14
Q

y-linked inheritance

A

affected males only

affected males transmit to all their sons

15
Q

mitochondrial inheritance

A

conditions can appear in every generation of a family
can affect both males and females
fathers do not pass these disorders to their daughters or sons

16
Q

examples of mitochondrial inheritance

A

leber’s hereditary optic neuropathy

leigh syndrome

17
Q

how are identical twins represented on a pedigree diagram?

A

like a triangle, joined with a line

18
Q

how are non-identical twins represented on a pedigree diagram?

A

1 line from the parents splits into 2

19
Q

why might a genetic test be considered?

A

to confirm a diagnosis
allow presymptomatic testing
provide an accurate assessment of genetic risk
change a treatment plan
give information about prognosis and management

20
Q

what are the different categories of genetic test?

A

diagnostic
carrier
prenatal
presymptomatic

21
Q

Diagnostic testing

A

to confirm or rule out a specific genetic or chromosomal condition which is suspected due to specific physical signs and symptoms
such as floppy babies
children with learning disabilities
cancer

22
Q

when can diagnostic testing be done?

A

can be performed before birth or at any time during a person’s life, but is not available for all genes or all genetic conditions
treatment/ counselling may depend on the gene/ type of mutation involved

23
Q

what is a floppy baby a sign of?

A

Prader willi syndrome
muscular dystrophy
spinal muscular atrophy

24
Q

what genetic test could be done for children with learning disabilities?

A

fragile X syndrome and CGH analysis for ploidy

25
Q

clinical clues of a genetic condition

A

there is patient or family history of an inherited condition
medical test results that suggest a possible genetic or chromosomal condition may be present
child presents demonstrating signs of developmental delay
woman aged 35 or over is or plans to become pregnant
woman has incurred a series of pregnancy losses or stillbirths
medical problems in the offspring of parents who are related by blood

26
Q

CADASIL

A

cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy

27
Q

what is CADASIL

A

most common hereditary vascular dementia

caused by mutations in exons 3 and 4 of the NOTCH3 gene

28
Q

symptoms of CADASIL

A

migraine
recurrent minor strokes
Family history of these 2

29
Q

presymptomatic testing

A

for unaffected individuals in families with a confirmed genetic disease with a known mutation
some genetic disorders are late onset and knowledge of genetic mutation can affect screening/ treatment. life style choices
e.g. cancer syndromes (breast and colon)
late onset neurological disease (Huntingtons)
there are significant ethical issues, so there are clear guidelines

30
Q

guideline for presymptomatic testing

A

individuals should be at 50% risk for autosomal dominant disease
usually over the age of 18 - unless a clinical intervention is possible

31
Q

what mutation causes huntington’s?

A

triplet repeat expansion in IT15 Huntingtin gene and shows anticipation

32
Q

what is anticipation?

A

as a genetic disorder is passed on to the next generation the symptoms become apparent at an earlier age with each generation

33
Q

Diagnosis of Huntington disease

A

no treatment

death occurs 15-20 years after diagnosis

34
Q

what are the implications for family members after a huntington diagnosis

A

presymptomatic testing now available for siblings and offspring
prior to presymptomatic testing genetic counselling is given
implications of a positive or negative result for patient and family discussed
follow-up appointment made to receive results

35
Q

what is a carrier

A

someone who has inherited one normal and one abnormal allele for a gene associated with the disorder which is either autosomal recessive or x-linked recessive. They are unaffected

36
Q

examples of carrier testing

A

mother of a boy affected by duchenne’s muscular dystrophy
siblings of a CF affected patient
people in certain ethnic groups with an increased risk of specific genetic conditions
available for chromosomal abnormalities

37
Q

what are the mutations for CF

A

p. Phe508 mutation

p. Gly551Asp

38
Q

who is prenatal genetic testing offered to?

A

women with increased risk of chromosome abnormality in offspring
couples who are known to carry a genetic disorder

39
Q

prenatal genetic tests

A

invasive with risk of miscarriage:

  • CVS - chorionic villous sampling
  • amniocentesis
  • NIPD - non-invasive prenatal diagnosis (possible for fetal sexing and small number of genetic disorders)
40
Q

what needs to known about prenatal genetic testing?

A
what will be tested for
chance of it occurring
risks of procedure
accuracy of test
potential outcomes of testing
option for termination 
no prenatal test can guarantee normality of the fetus - not possible to test for every disease