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Comment
. 2020 Apr;69(4):790-792.
doi: 10.1136/gutjnl-2019-318751. Epub 2019 Apr 20.

Novel p.K374E variant of CPA1 causes misfolding-induced hereditary pancreatitis with autosomal dominant inheritance

Balázs Csaba Németh  1   2 , Anna Orekhova  3 , Wenying Zhang  4   5 , Shannon A Nortman  5 , Tyler Thompson  6 , Péter Hegyi  2   7 , Maisam Abu-El-Haija  4   6
Affiliations
Comment

Novel p.K374E variant of CPA1 causes misfolding-induced hereditary pancreatitis with autosomal dominant inheritance

Balázs Csaba Németh et al. Gut. 2020 Apr.
No abstract available

Keywords: pancreas; pancreatic enzymes; pancreatitis.

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Conflict of interest statement

Competing interests: None declared.

Figures

Figure 1
Figure 1
(A) Pedigree of a family with hereditary pancreatitis associated with the CPA1 c.1120A>G (p.K374E) variant. The arrow points to the index patient with acute recurrent pancreatitis. Solid black symbols indicate affected family members with acute recurrent pancreatitis; the solid grey symbol indicates the subject with one acute pancreatitis attack. The open symbol with a dot designates unaffected carrier. (B) Electropherogram of a heterozygous carrier of the c.1120A>G CPA1 variant.
Figure 2
Figure 2
Effect of the p.Asn256Lys (N256K) and p.Lys374Glu (K374E) variants on CPA1 secretion, intracellular CPA1 levels and endoplasmic reticulum (ER) stress markers in transiently transfected HEK 293T cells. (A) Secretion of CPA1. Duplicate samples of 400 μL growth medium were analysed by sodium dodecyl sulfate polyacrylamide gel electrophoresis (SDS-PAGE) and Coomassie Blue staining. (B) Intracellular and secreted levels of CPA1 were evaluated by western blotting. Twenty micrograms total cell lysate protein and 2 μL of 2 mL conditioned media were loaded in duplicates. Two gels of cell lysate and two gels of growth medium were run with the same set of samples. The membranes were probed separately for CPA1 and actin. (C) Expression of BiP (HSPA5) mRNA was measured by quantitative reverse transcription (RT) PCR. Average of three independent experiments with SD is shown. (D) RT-PCR of XBP1 splicing was visualised by 2% agarose gel electrophoresis with ethidium bromide staining. A representative gel of three independent experiments is shown. For further experimental details see Witt et al.
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References

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