Clinical Genetics

Question 1

Types of mutations

Answer 1

Missense = C replaced with B and are not always pathogenic

Nonsense = deletion of small part of gene which makes the protein sequence stop (premature truncation)

Frame shift = loss of one code, so the whole sequence is shifted – so makes the whole rest of the sequence not read well.
- Can be pathogenic in some cases

Duplication = repeated codon
-Can be pathogenic in some cases

Insertion = added codon so can cause premature truncation (pathogenic)

Question 2

What increases the probability of a genetic disorder?

Answer 2

Family history of a genetic disorder

Consanguinity = being blood related increases the risk that both parents are carriers of the same recessive allele

Certain conditions are associated with particular ancestral populations e.g. Ashkenazi Jewish and tay sachs, northern Europeans and cystic fibrosis, Asians and thalassemia

Risk of non-disjunction and chromosomal aneupoloidy increases with maternal age due to wear and tear on the machinery for cell division through time

Risks of new mutations increase with increasing paternal age due to the increasing number of germ cell divisions in each spermatogonium

Environmental factors include smoking, certain medications, and occupations

Question 3

Three scans safe for foetus and mother

Answer 3

Scan to determine gestational age and number of foetuses

Foetal nuchal translucency scan at 11-14 weeks gestation.

• This measures the thickness of the fluid under skin at the back of the neck and is often combined with maternal biochemical blood tests, age and weight
• Determines the probability of the foetus having Down’s syndrome but can also indicate other chromosomal disorders
• If this is greater than 1 in 150 they will be offered further diagnostic testing

Foetal anomaly scan at 18-20 weeks’ gestation
- This is a detailed scan for structural anomalies or conditions requiring treatment

Question 4

what is newborn screening?

Answer 4

Involves a blood sample at birth, which is tested for metabolic conditions in which early detection and treatment will improve long-term outcome.

This includes conditions such as PKU, congenital hypothyroidism, sickle cell disease, cystic fibrosis, and MCADD.

Question 5

Chorionic villous sampling

Answer 5

Involves taking a biopsy of the placenta in the first trimester, typically from week 10-12.

This can be performed transcervically or transabdominally, and enables chromosomal and DNA analysis.

It carries a 1-2% risk of miscarriage and isn’t performed prior to 9 weeks due to the risk of limb defects

Question 6

Amniocentesis

Answer 6

Performed at 16 weeks, and removes fluid and cells from the amniotic sac surrounding the foetus.

The fluid can be used to assess neural tube defects, and the cells to look at genetic anomalies.

This carries a 0.5-1% risk of miscarriage