The primary objective of this study is to describe the transcriptional impact of R178, R257, R40 or A136 variants of the ACTG2 gene on iPS differentiation mechanisms up to organoids derived from PIPO patient samples versus those derived from control / WT patients (generation of IPS from cultured cell lines), at different stages of their experimental ex vivo development.
Minor or adult patient ≥ 4 years of age
Patient with PIPO before age 18
Male or female
Patient with PIPO meeting at least 2 of the ESPGHAN criteria (Thapar et al 2018) and carrying the R178, R257, R40 or A136 mutation of the ACTG2 gene.
Patients with a history of radiotherapy treatment
Patient with lymphocyte lineage damage
Factorial
Biopsy
Procedure/SurgeryA skin biopsy and a blood sample will be taken to culture the iPS cells and intestinal organoids.
Description of the transcriptional impact of R178, R257, R40 or A136 variants of the ACTG2 gene
Difference in transcript expression (%) in RNASeq transcriptomic analysis between samples carrying the R178, R257, R40 or A136 variants of the ACTG2 gene on the differentiation mechanisms of iPS up to organoids derived from PIPO patient samples versus those derived from control patients
Evaluate the impact of R178, R257, R40 or A136 variants of the ACTG2 gene on gastrointestinal contractile function between mutant versus WT organoids.
Difference (%) in isometric contraction force between mutant versus WT organoids by electrical stimulation and specific agonist.
Evaluate the immunofluorescence labeling differential between mutant and WT cells from IPS and organoids
Difference in fluorescence (%) between mutant and WT cells as cell stages from iPS to organoids
Evaluate the impact of R178, R257, R40 or A136 mutations of the ACTG2 gene on the actin network of fibroblasts derived from skin samples of diseased patients versus those of WTpatients.
Difference in actin network labeling by immunofluorescence (%) between skin fibroblasts from PIPO and WT patients.
Evaluate the effect of reversion of the R178, R257, R40 or A136 mutation versus WT on functionality and contractility during differentiation of cells into organoids.
Difference in isometric contraction strength (%) between mutant versus WT versus revertant organoids via specific agonist and electrical stimulation.
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