Characteristics of the test: (includes 1 gene)

RET (OMIM # 164761)

Main characteristics of the clinical phenotype:

Hirschsprung's disease is characterized by a congenital absence of nerve endings in part or all of the large intestine, and in some cases also in preceding segments of the gastrointestinal tract. This results in permanent contraction of the musculature of the affected part of the gastrointestinal tract and distension of the preceding segments due to accumulation of intestinal contents. The disease usually manifests itself immediately after birth, less often up to 10 years of age in the form of defecation difficulties. The severity of the disease depends on the age of first manifestation in cases where the cause is a newly occurring mutation in one of the genes responsible for the disease.

Indications  for referral:
Genetic testing is recommended in order to assess the risk of transmitting the disease in the offspring. About 50% of familial cases and 15% to 35% of sporadic cases of the disease are thought to carry a loss-of-function mutation in the coding region of the RET gene. The penetrance (the chance of clinical manifestation) of the mutations is about 65% in males and 45% in females.

Interpretation of results:

Method: Sanger sequencing

The method involves bi-directional DNA sequencing of all coding exons and intron-exon boundaries of the MLH1, MSH2 and MSH6 genes. The laboratory offers single exon or exon pair sequencing in relatives of patients to determine the carrier status in cases where the mutation is known (Tests #182 and 183).

Sensitivity of the method: 99.5%

What does the test involve?

· DNA isolation and sample storage.

· Direct sequencing of target genes/gene regions to detect pathogenic mutations.

· Forming a written result of the genetic test.

· Diagnostic interpretation of results and genetic counseling.

Biological material: Fresh or FFPE tumor tissue, or DNA isolated from Fresh or FFPE tumor tissue. For more information, please read the "Biological material requirements and shipping information" carefully.