5: Phenotypic variability Flashcards
Phenotypic variability is
the variation of gene expression in the same disease in different individuals
- may not have same symptoms or presentations
5 causes of phenotypic variability
Environment e.g low iron intake
Sex - expression of a gene varies by sex e.g hereditary haemochromatosis
Modifiers - expression of gene directly affected by presence of other genes e.g CF
Mutation - different mutated subtypes of same disease have different presentations e.g Duchenne vs Becker dystrophy
Unstable - trinucleotide repeat disorders - incr. number of nucleotide repeats (>27) cause more severe phenotypes throughout generations e.g Huntingtons more severe in future generations
Genetic testing is carried out as a part of
pre-natal screening
When are genetic tests carried out in pregnancy
11-14 week : dating pregnancy, diagnose multiple pregnancy, major foetal abormalities, early miscarriage. assess risk of downs syndrome (nuchal translucency)
20-22 week : look for 11 rare conditions, more detailed- bones, heart, brain, spinal cord, face, kidneys
If any anomalies are found in pre-natal screening what two paths can be taken
Non- invasive test
Invasive tests
Non-invasive tests include
Maternal blood test
Cell free foetal DNA (cffDNA)
Invasive tests include
Chronic villus sampling (CVS) (11-14 weeks)
Amniocentesis (16+ weeks)
Nuchal Translucency tests
don’t indicate chromosomal abnormality, just identify higher risk of one
- screening test not diagnostic test
In a nuchal translucency test
Fluid from the back of the fetal neck collected between 10-14 weeks
Increase nuchal translucency test result can indicate
> 3mm
chromosome abnormalities
NT + maternal age detects up to 75% of down syndrome with 5% false postive rate
Birth defects associated with incr. nuchal translucency results
cardiac anomalies
pulmonary defects (diaphragmatic hernia)
renal defects
abdominal wall defects
- skeletal dysplasia
prenatal testing is arranged following
abnormal findings at nuchal/mid-trimester scan and in women with high risk of down syndrome or previous history of genetic disease
4 aims of prenatal testing
to inform and prepare parents for birth of an affected baby
to allow possible in utero treatment
to aid managing the remainder of the pregnancy
to allow termination of affected fetus
Maternal serum screening is an example of
Non-invasive genetic testing
not fully accurate
Maternal serum screening tests for
maternal serum markers in the blood to detect increased risk of fetal trisomy 21/18 and neural tube defects
Combined MSS test
1st trimester (11-14 weeks) tests for hCG, PAPP A
Second MSS test
2nd trimester (16-20 weeks) tests for hCG, AFP, UE3
Cell-Free foetal DNA test is an example of a
Non-invasive genetic test
usually carried out privately
A cell-free foetal DNA test analyses
placental DNA in maternal plasma
first detectable at 4-5 weeks but most accurate at 9 weeks
Chorionic Villus Sampling is an example of
an invasive genetic test
Chorionic Villus Sampling consists of
Transabdominal/vaginal sample taken of chorionic villi as it contains some foetal DNA
Allows for earlier results than amnio for abortion, but 1-2% risk of miscarriage so only done if risk is known
Amniocentesis is an example of an
invasive genetic test
Amniocentesis consists of
sample of cells taken from amniotic fluid containing foetal cells
Risk of Rh sensitization and infection
1% risk of miscarriage
What invasive test is carried out first
Chorionic Villus sampling
