Pancreatitis

Gene: CFTR

Green List (high evidence)

Comment when marking as ready: As discussed in the GMS Gastrohepatology Specialist Test Group webex call 14th Jan 2019: The Specialist Test Group agreed that there is enough evidence to rate this gene green.

Created: 24 Jan 2019, 4:19 p.m.

Initial gene list and info collated by Miranda Durkie Sheffield Diagnostic Genetics Service December 2018 on behalf of the GMS Gastrohepatology specialist test group. Gene Symbol submitted: CFTR; Suggested intial gene rating: Green; Evidence for inclusion: none given; Evidence for exclusion: none given; Technical notes (e.g. non-coding/CNV mutations requiring coverage?): none given

Created: 7 Jan 2019, 4:15 p.m.

Comment on list classification: This gene has been promoted from Amber to Green, for the biallelic mode of inheritance, due to comments from Dr Ellen Thomas that exocrine pancreas dysfunction is an indication for diagnostic Cystic Fibrosis testing, and therefore this panel should cover the CFTR gene.

Created: 7 Dec 2018, 9:23 a.m.

Comment on mode of inheritance: Changed to the biallelic form.

Created: 7 Dec 2018, 9:20 a.m.

Green List (high evidence)

Atypical or late presentations of CF with pancreatitis and exocrine pancreatic dysfunction are recognised; this forms part of the diagnostic work-up for unexplained pancreatitis.

Created: 6 Dec 2018, 8:30 p.m.

Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal

Phenotypes
Cystic fibrosis

Variants in this GENE are reported as part of current diagnostic practice

Comment on list classification: Rating Amber based on feedback from Genomics England clinical team.

Created: 2 Oct 2018, 3:36 p.m.

Checking with Genomics England Clinical team as to the correct rating for this gene.

Created: 13 Sep 2018, 1:30 p.m.

In OMIM CFTR is associated with a susceptibility to {Pancreatitis, hereditary}.

Numerous candidate gene association studies have shown that CFTR variants are overrepresented in chronic pancreatitis (PMID: 9725921;15987793;16134171;16193325;11729110;23951356;22427236;25033378). These are reviewed by Ooi and Durie (2012) (PMID: 22658665) and Hegyi et al (2016)(PMID: 26856995).

In a review of hereditary pancreatitis Raphael and Willingham (2016) (PMID: 27555793) state that autosomal recessive inheritance of severe homozygous mutations, such as F508-delta/F508-delta, results in the typical multisystem cystic fibrosis phenotype that most often includes early-onset pancreatic insufficiency. Patients with this type of inheritance rarely develop recurrent acute pancreatitis in the form of HP (PMID: 1345141). Conversely, inheritance of one of the mild variants of CFTR, such as the R75Q mutation, is associated with a more limited cystic fibrosis syndrome and a greater incidence of pancreatitis (PMID: 15749233). Additionally, nine CFTR mutations associated with a deficiency in bicarbonate conductance (known as CFTR–BD mutations) were identified carrying a risk of acute and chronic pancreatitis in the setting of an otherwise mild cystic fibrosis syndrome (PMID: 25033378 ). Some CFTR mutations can be inherited in a complex-type pattern. When a patient is heterozygous with, for example, one CFTR mutation and an additional genetic mutation, such as SPINK1 or CTRC, the risk of pancreatitis is increased (PMID: 20977904;22427236).

No information in Gene2Phenotype.

Created: 13 Sep 2018, 1:13 p.m.

Mode of inheritance
MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown

Phenotypes
{Pancreatitis, hereditary} 167800

Publications

• 9725921
• 15987793
• 16134171
• 16193325
• 11729110
• 23951356
• 22427236
• 25033378
• 22658665
• 26856995
• 27555793
• 1345141
• 15749233
• 25033378
• 20977904
• 22427236

Green List (high evidence)