Pancreatitis

Gene: CTRC

Green List (high evidence)

CTRC will remain amber until further evidence can be provided before this will be promoted to green gene status.

Created: 4 Sep 2019, 9:35 a.m. | Last Modified: 4 Sep 2019, 9:35 a.m.

Panel Version: 1.12

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: CTRC; 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: Demoting this gene from Green to Amber as it seems to be a susceptibility gene, rather than an isolated cause of inherited pancreatitis.

Created: 6 Dec 2018, 1:14 p.m.

Comment on mode of inheritance: From OMIM

Created: 12 Sep 2018, 10:44 p.m.

Comment on list classification: More than 3 cases of plausible disease causing variants found in association with this disorder.

Created: 12 Sep 2018, 10:43 p.m.

In OMIM the CTRC gene is associated with {Pancreatitis, chronic, susceptibility to}.

Rosendahl et al. (2008) (PMID: 18059268) analysed CTRC in 901 German subjects with idiopathic or hereditary chronic pancreatitis. Two alterations in this gene, R254W and K247_R254del, were significantly overrepresented in the pancreatitis group. A replication study identified these 2 variants in 10 of 348 (2.9%) individuals with alcoholic chronic pancreatitis but only 3 of 432 (0.7%) subjects with alcoholic liver disease. CTRC variants were also found in 10 of 71 (14.1%) Indian subjects with tropical pancreatitis but only 1 of 84 (1.2%) healthy controls. Functional analysis of these CTRC variants showed impaired activity and/or reduced secretion.

Masson et al. (2008) (PMID:18172691) sequenced the CTRC gene in 287 white French patients with idiopathic chronic pancreatitis and 350 controls and identified 2 common variants and 19 rare variants. The combined frequency of the rare variants in patients with sporadic chronic pancreatitis was significantly higher than that of controls (12% versus 1.1%; OR, 11.8; p less than 10(-6)).

More recently Giefer et al. (2017)(PMID: 28502372) looking at 342 children (< 19 years old) with pediatric acute recurrent pancreatitis or chronic pancreatitis found that CTRC mutations were more common among those with early onset pancreatitis (EOP) (< 6 years old) (14%) than in the later onset cohorts (p=0.01). Seven different CTRC mutations were found and the p.R254W mutation was identified in three patients, all of whom had EOP. Only 2 patients with onset of disease at age 6 years or older were found to have a CTRC mutation.

No information from Gene2Phenotype.

Created: 12 Sep 2018, 10:42 p.m.

Green List (high evidence)