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Gastroenterology

Haemochromatosis (HFE)

Genetic Haemochromatosis (GH) is an autosomal recessive disorder. The gene for GH, called HFE has been identified. Two missense mutations have been described. Greater than 90% of GH patients are homozygous for the C282Y mutation. The significance of the second mutation, H63D, is less clear.  H63D, either as heterozygous, or homozygous, does not appear to be associated with a significant risk of iron overload. However, it is possible that compound heterozygotes (ie one copy of H63D and one copy of C282Y) may express iron overload. This is usually not as severe as C282Y homozygotes, but may be clinically significant.

HLA DQ2/8 Coeliac Exclusion

HLA gene testing is useful in cases where the diagnosis of coeliac disease remains unclear. Over 99% of patients affected by coeliac disease have the HLA DQ2, HLA DQ8, or parts of these genes. Therefore, a negative test for these genes effectively rules out coeliac disease. The gene test on its own cannot diagnose coeliac disease – only 1 in 30 people who have HLA DQ2 or HLA DQ8 will develop coeliac disease.

Proton Pump Inhibitor Predict

The CYP2C19 gene codes for an enzyme that metabolizes approximately 10-15% of all drugs, including many of the proton pump inhibitors.  Detecting variants of the CYP2C19 gene that cause altered enzymatic activity can identify patients who may be at increased risk of having adverse drug reactions or therapeutic failure to standard dosages of CYP2C19 substrates.

TPMT

The TPMT gene codes for an enzyme that carries out S-methylation. This function is of particular importance because it is critical for metabolizing drugs called thiopurines. These drugs, which include 6-thioguanine, 6-mercaptopurine, and azathioprine, inhibit the body's immune system. They are used to treat several forms of cancer and other disorders involving immune system malfunction, such as Crohn disease and rheumatoid arthritis. Thiopurine drugs are also used in organ transplant recipients to help prevent the immune system from attacking the transplanted organ.Once inside the body, thiopurine drugs are converted to toxic compounds that kill immune system cells in the bone marrow. The TPMT enzyme "turns off" thiopurine drugs by metabolizing them to inactive, nontoxic compounds. Genetic variations in the TPMT gene cause TPMT enzyme deficiency. Without enough of this enzyme, the body cannot "turn off" thiopurine drugs by metabolizing them into inactive compounds. The drugs stay in the body longer and continue to destroy cells unchecked, which leads to bone marrow damage (hematopoietic toxicity). This damage causes myelosuppression, which is an inability of the bone marrow to make enough red blood cells, white blood cells, and platelets.

Colorectal Cancer Gene Panel

Molecular characterisation of solid tumours
is now playing a central role in patient management. The Australian Clinical Labs Colorectal Cancer Somatic Mutation panel is a Next Generation Sequencing (NGS) testing panel designed to investigate multiple relevant mutations in formalin fixed paraffin embedded colorectal cancer samples. This panel detects mutations within oncogenes and tumour suppressor genes that are frequently mutated in colorectal cancer that can aid clinicians to select the most appropriate treatment for their patients. Genes sequenced in this panels are kRAS, nRAS, BRAF, PIK3CA, PTEN and AKT1.

Gilbert Disease

Gilbert syndrome is a benign cause of mild unconjugated hyperbilirubinemia. The prevalence is 12% in Caucasian males and 5% in Caucasian females. The syndrome is caused by impaired hepatic glucuronidation of bilirubin by UDP-glucuronosyltransferase (UGT1A1).  Most cases are due to an extra TA dinucleotide in the TA repeat sequence in the promoter for this gene.