Details

Autor(en) / Beteiligte

• Masson, Emmanuelle
• Rebours, Vinciane
• Buscail, Louis
• Frete, Frédérique
• Pagenault, Mael
• Lachaux, Alain
• Chevaux, Jean‐Baptiste
• Génin, Emmanuelle
• Cooper, David N.
• Férec, Claude
• Chen, Jian‐Min

Titel

The reversion variant (p.Arg90Leu) at the evolutionarily adaptive p.Arg90 site in CELA3B predisposes to chronic pancreatitis

Ist Teil von

• Human mutation, 2021-04, Vol.42 (4), p.385-391

Ort / Verlag

United States: Hindawi Limited

Erscheinungsjahr

2021

Quelle

MEDLINE

Beschreibungen/Notizen

• 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 obvious 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 four patients but no controls, and affects the same amino acid as p.Arg90Cys, serves to revert p.Arg90 to the human elastase ancestral allele. As p.Arg90Leu has previously been shown to exert a similar functional effect to that of 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.