0319 - Genetics of GI Disorders

Question 1

What is the underlying cause of Gilbert’s Syndrome?

Answer 1

The gene that codes for UDP-glucuronyltransferase 1A1 (conjugating Bilirubin), has an additional repeat of TAA, leading to enzyme levels 30% of normal.

Essentially, you only have 30% of the protein that can conjugate bilirubin, hence buildup of unconjugated bilirubin.

Question 2

What is the genetic cause of familial adenomatous polyposis?

Answer 2

Mutations in the tumour suppressor gene adenomatous polyposis coli (APC) - autosomal dominant with near complete penetrance of polyps.

25% of FAP do not have family history, and each mutation is unique, so no way to test for a particular mutation.

Question 3

What is the genetic basis of Crohn’s disease?

Answer 3

Mutations in the NOD2 (bacterial recognition) gene, however extremely low penetrance (03-1.5%). Suggests a role for more genes or environmental factors.

Question 4

Briefly outline the genetics of haemochromatosis

Answer 4

Usually autosomal recessive - well characterised mutation that can be tested for.

Question 5

Briefly outline the genetics of Gilbert’s syndrome

Answer 5

Autosomal recessive, well characterised mutation in the bilirubin conjugation protein UDP glucuronyltransferase 1A1.

Question 6

Briefly outline the genetics of CRC

Answer 6

Familial forms follow Mendelian inheritance and two-hit hypothesis.

Sporadic forms also arise (75% of cases).