Pancreatitis Plus Panel (CFTR, PRSS1, SPINK1, CTRC sequence)

Chronic pancreatitis (CP) is characterized by recurring inflammatory attacks that gradually cause irreversible damage to the pancreas and surrounding tissue.   Risk factors for chronic pancreatitis fall into the following categories: toxic metabolic, idiopathic, autoimmune, obstructive, recurrent, and genetic.   

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Chronic pancreatitis (CP) is characterized by recurring inflammatory attacks that gradually cause irreversible damage to the pancreas and surrounding tissue.   Risk factors for chronic pancreatitis fall into the following categories: toxic metabolic, idiopathic, autoimmune, obstructive, recurrent, and genetic.   

Alcoholism is the primary cause of chronic pancreatitis, but in some cases, chronic pancreatitis is inherited.  Hereditary pancreatitis usually begins in childhood and is an autosomal dominant condition caused by mutations in the major pancreatic gene PRSS1.   At least 17 mutations have been described (R122H the most common) on the PRSS1 gene that either cause or are associated with chronic pancreatitis.   SPINK1 is a modifier gene, the normal function of which is to inhibit potential trypsin activity in the pancreas.   Mutations in SPINK1 impair this protective function and have been identified as risk factors in idiopathic, familial, tropical and alcoholic pancreatitis.   At least 14 mutations have been identified (N34S the most common) on the SPINK1 gene.  

Cystic Fibrosis (CF) is an autosomal recessive disorder and has an incidence of 1/3200 births in the U.S and a carrier frequency of 1/25 for Non-Hispanic Caucasian.   Some forms of CF are also known to cause pancreatitis.  Chymotrypsin C, encoded by the CTRC gene, normally functions to prevent premature trypsinogen activation in the pancreas and to permit trypsin degradation in the gut.  Variants in the CTRC gene that reduce Chymotrypsin C’s activity or production have been detected with increased frequency in some patients with idiopathic chronic pancreatitis.  

The Ambry Test: Pancreatitis Plus Panel includes gene sequence analysis of the PRSS1, SPINK1, CFTR and CTRC genes.  Sequence analysis detects approximately 99% of mutations in PRSS1, SPINK1 and CTRC, and approximately 97-98% of mutations in CFTR (analytical sensitivity).

Disease Name 
Pancreatitis
Disease Information 

Chronic pancreatitis (CP) is characterized by recurring inflammatory attacks that gradually cause irreversible damage to the pancreas and surrounding tissue.   Risk factors for chronic pancreatitis fall into the following categories: toxic metabolic, idiopathic, autoimmune, obstructive, recurrent, and genetic.   Alcoholism is the primary cause of chronic pancreatitis, but in some cases, chronic pancreatitis is inherited.  Hereditary pancreatitis usually begins in childhood and is an autosomal dominant condition caused by mutations in the major pancreatic gene PRSS1.   At least 17 mutations have been described (R122H the most common) on the PRSS1 gene that either cause or are associated with chronic pancreatitis.   SPINK1 is a modifier gene, the normal function of which is to inhibit potential trypsin activity in the pancreas.   Mutations in SPINK1 impair this protective function and have been identified as risk factors in idiopathic, familial, tropical and alcoholic pancreatitis.   At least 14 mutations have been identified (N34S the most common) on the SPINK1 gene.  

Cystic Fibrosis (CF) is an autosomal recessive disorder and has an incidence of 1/3200 births in the U.S and a carrier frequency of 1/25 for Non-Hispanic Caucasian.   Some forms of CF are also known to cause pancreatitis.  Chymotrypsin C, encoded by the CTRC gene, normally functions to prevent premature trypsinogen activation in the pancreas and to permit trypsin degradation in the gut.  Variants in the CTRC gene that reduce Chymotrypsin C’s activity or production have been detected with increased frequency in some patients with idiopathic chronic pancreatitis.  

Testing Benefits & Indication 

Pancreatitis Panel Plus is useful for diagnostic confirmation in symptomatic individuals, and for testing of at-risk asymptomatic family members.  Testing can help avoid repeated diagnostic tests and help guide recommendations for surveillance and reducing exposure to environmental risk factors such as smoking and alcohol use. Sequence analysis of individual genes alone or in combination is also available.  Specific mutation analysis of individual mutations identified previously in a family member is also available. Deletion/duplication analysis of CFTR is available upon request.

Test Description 

Sequence variations in the following CFTR promoter region, exons, and critical intronic regions that could contribute to CF are analyzed using the Ambry Test: CF: 983 bases of 5' untranslated region (UTR) and exons 1 to 24 (a total of 27 exons), plus at least 20 bases into the 5' and 3' ends of all the introns. CFTR poly T status, TG repeat, intron 19’s 3849+10kbC>T mutation, and intron 11’s 1811+1634A>G mutation (aka 1811+1.6kbA>G) are also analyzed. Sequence variations in the following exons and critical intronic regions that could contribute to chronic pancreatitis (CP) are analyzed using the Ambry Test: PRSS1 exons 1 to 5, plus at least 20 bases into the 5' and 3' ends of all the introns.  In addition, the PRSS1 gene is analyzed in the 5' UTR at -28 nucleotides for a known deletion mutation.  Sequence variations in the following exons and critical intronic regions that could contribute to CP are analyzed using the Ambry Test: SPINK1 exons 1 to 4, plus at least 20 bases into the 5' and 3' ends of all the introns.  In addition, the SPINK1 gene is analyzed in the 5' UTR up to at least the -215 position and intron 3 region up to nucleotide +184. Sequence variations in the following exons and critical intronic regions that could contribute to CP are analyzed using the Ambry Test: CTRC exons 1-8 plus at least 20 bases into the 5’ and 3’ ends of all the introns are analyzed. In addition, the CTRC 5’UTR region is analyzed up to 60 bases upstream from the start codon. The following sites are used to search for previously described variants in the CFTR, PRSS1, SPINK1, and CTRC genes: HGMD and online search engines (i.e. PubMed).  Toronto Sick Children's CF database and Leipzig Databases are also used to search for previously described CFTR and PRSS1/SPINK1 mutations and polymorphisms, respectively.

Mutation Detection Rate 

Sequence analysis detects approximately 99% of mutations in PRSS1, SPINK1 and CTRC, and it detects 97-98% of mutations in CFTR.

Specimen Requirements 

Blood Spot: Note: blood spots are not accepted for PRSS1 analysis; they are acceptable for CFTR, SPINK1, and CTRC. Minimum of one complete spot approximately 0.5 inch in diameter on S&S 903 collection paper or similar. Store in a clean plastic bag at room temperature. Ship at room temperature.

Billing Codes 

Test Code

Technique
8022 Pancreatitis Plus Panel (CFTR, PRSS1, SPINK1, CTRC)
8040 Pancreatitis AMPLIFIED (CFTR with deletion/duplication,PRSS1, SPINK1)
8020 Pancreatitis (CFTR, PRSS1, SPINK1)
1100 PRSS1
1120 SPINK1
1660 CTRC
  Specific mutation analysis, any gene

 

Turnaround Time 
Technique Days
Pancreatitis Plus Panel (CFTR, PRSS1, SPINK1, CTRC) 14-28
Pancreatitis AMPLIFIED (CFTR with deletion/duplication,PRSS1, SPINK1) 14-35
Pancreatitis (CFTR, PRSS1, SPINK1) 14-28
PRSS1 Gene Sequence Analysis 14-28
SPINK1 Gene Sequence Analysis 14-28
CTRC Gene Sequence Analysis 14-21
Specific mutation analysis, any gene 7-14

 

Specialty 
Genes 
References 

Reference available upon request.