Overview
BPAN (beta-propeller associated neurodegeneration) is caused by mutations in the autophagy gene WDR45, also known as WIPI4, located on the X chromosome. Mutations in WDR45 result in neurodevelopmental impairment in girls and early-onset epileptic encephalopathy in boys, followed by neurodegeneration in adults (SENDA). This condition is a subtype of neurodegeneration with brain iron overload (NBIA). BPAN is the most recently identified subtype of NBIA and it is important to understand how mutations in WDR45, present in patients∙e∙s, cause cell death.
Autophagy is a cell survival mechanism responsible for the degradation and recycling of cell contents. It has been proposed that autophagy becomes less efficient during normal aging, which could cause neuronal death and thus lead to neurodegeneration.
Reduced autophagic activity has been observed in lymphoblastic cells of BPAN patients and in brains of KO mice for WDR45. The current hypothesis to explain the pathology associated with WDR45 mutations is that a defect in autophagy leads to neurodegeneration. However, we do not know if the autophagy defect is causal or if other deregulations of cellular responses contribute to neurodegeneration. Preliminary results from Pr. Bertrand Mollereau's team suggest that a global deregulation of cellular stress responses may be induced in patient cells. This includes in particular the endoplasmic reticulum response to stress (UPR response) as well as lipid storage mechanisms.
The investigators hypothesize that cells from patients carrying pathogenic variants of WDR45 will exhibit deregulation of cellular stress response pathways.
Eligibility
Inclusion Criteria:
- Weight ≥ 12.5kg
- Presence of WDR45 pathogenic variant gene
- Children or adults (no upper limit for age)
- Patient under guardianship could be included if they are assisted by their guardian/adviser in compliance with article L1122-2 of the Public Health Code by virtue of the protection of vulnerable populations
Exclusion Criteria:
- According to the order of 12/04/2018 of the Public Health Code : Weight ≤ 12.5 kg for a
10mL sample or For 2 male and 2 female Lyon patients : Weight ≤ 25 kg for a 20mL sample
- No French Social Insurance Regimen
- Refusal of participation by the legal representative of the patient