IRF4 haploinsufficiency in a family with Whipple's disease
- Guerin, Antoine
- Kerner, Gaspard
- Marr, Nico
- Markle, Janet G.
- Fenollar, Florence
- Wong, Natalie
- Boughorbel, Sabri
- Avery, Danielle T.
- Ma, Cindy S.
- Bougarn, Salim
- Bouaziz, Matthieu
- Beziat, Vivien
- Della Mina, Erika
- Oleaga-Quintas, Carmen
- Lazarov, Tomi
- Worley, Lisa
- Nguyen, Tina
- Patin, Etienne
- Deswarte, Caroline
- Martinez-Barricarte, Ruben
- Boucherit, Soraya
- Ayral, Xavier
- Edouard, Sophie
- Boisson-Dupuis, Stephanie
- Rattina, Vimel
- Bigio, Benedetta
- Vogt, Guillaume
- Geissmann, Frederic
- Quintana-Murci, Lluis
- Chaussabel, Damien
- Tangye, Stuart G.
- Raoult, Didier
- Abel, Laurent
- Bustamante, Jacinta
- Casanova, Jean-Laurent
DOIAbstract
International audienceMost humans are exposed to Tropheryma whipplei (Tw). Whipple's disease (WD) strikes only a small minority of individuals infected with Tw (<0.01%), whereas asymptomatic chronic carriage is more common (<25%). We studied a multiplex kindred, containing four WD patients and five healthy Tw chronic carriers. We hypothesized that WD displays autosomal dominant (AD) inheritance, with age-dependent incomplete penetrance. We identified a single very rare non-synonymous mutation in the four patients: the private R98W variant of IRF4, a transcription factor involved in immunity. The five Tw carriers were younger, and also heterozygous for R98W. We found that R98W was loss-of-function, modified the transcriptome of heterozygous ...
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