Pre-symptomatic and Pre-natal Diagnosis of Genetic Disease

Question 1

What does raised nuchal translucency indicate?

Answer 1

• Increased risk of chromosomal abnormalities.
• E.g. trisomy 21.
• Also congenital heart disease and other syndromes.

Question 2

Outline the inheritance of triplet repeat expansion disorders.

Answer 2

• Gene/intron contains an unstable section consisting of triplet repeats - e.g. CAG in Huntington’s.
• This is a subset of unstable microsatellite repeats.
• Number of triplets may expand when transmitted from parent to child.
• Number of repeats varies along a spectrum - normal, intermediate, affected.
• E.g. Huntington’s - affected if more than 35 CAG repeats.
• May lead to genetic “anticipation” in families - age of onset of disease decreases due to further triplet repeat expansion.

Question 3

Describe how prenatal exclusion testing is used in Huntington’s disease.

Answer 3

• Determines if embryo is high or low risk for HD.
• This is calculated by looking at the grandparental hapolotype.
• E.g. if embryo has 1 allele from affected grandparent, there is 50% risk of HD - high risk.