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The reversion variant (p.Arg90Leu) at the evolutionarily adaptive p.Arg90 site in CELA3B predisposes to chronic pancreatitis
- Source :
- Human mutationREFERENCES. 42(4)
- Publication Year :
- 2021
-
Abstract
- A gain-of-function missense variant in the CELA3B gene, p.Arg90Cys (c.268C>T), has recently been reported to cause pancreatitis in an extended pedigree. Herein, we sequenced the CELA3B gene in 644 genetically unexplained French chronic pancreatitis (CP) patients (all unrelated) and 566 controls. No predicted loss-of-function variants were identified. None of the six low frequency or common missense variants detected showed significant association with CP. Nor did the aggregate rare/very rare missense variants (n=14) show any significant association with CP. However, p.Arg90Leu (c.269G>T), which was found in 4 patients but no controls and affects the same amino acid as p.Arg90Cys, serves to revert p.Arg90 to the human elastase ancestral allele. Since p.Arg90Leu has previously been shown to exert a similar functional effect to p.Arg90Cys, our findings not only confirm the involvement of CELA3B in the etiology of CP but also pinpoint a new evolutionarily adaptive site in the human genome.
- Subjects :
- Genetics
0303 health sciences
Base Sequence
Pancreatic Elastase
030305 genetics & heredity
Elastase
Reversion
Mutation, Missense
Biology
medicine.disease
Pedigree
03 medical and health sciences
Pancreatitis, Chronic
Etiology
medicine
Missense mutation
Pancreatitis
Humans
Human genome
Gene conversion
Allele
Gene
Genetics (clinical)
030304 developmental biology
Subjects
Details
- ISSN :
- 10981004 and 10597794
- Volume :
- 42
- Issue :
- 4
- Database :
- OpenAIRE
- Journal :
- Human mutationREFERENCES
- Accession number :
- edsair.doi.dedup.....b6d0b79d05cb9d482497ae2287bd4a0f