# Outline
## NBIA
Neurogeneration with brain iron accumulation =  progressive extrapyramidal with accumulation of iron in the brain on MRI, usually basal ganglia
85% have a genetic basis and most of these are due to 4 genes: *PKAN2*,*PLA2G6*, *C19orf12*, *WDR45*. In total, 9 genes are reported.
Classification is based on genes.
Clincal and MRI may orient to a specific gene (Table 19.2 in [@haylick2018]).
Rare: PKAN is half of the case and its estimated prevalence is 1/1 000 000 [@gregory2002]
## Beta-propeller protein associated neurodegeneration
phenotype described in Gregory2002, Gregory2019.
Genetic basis in Haack2012, with phenotype detailed in Haylick2013 (20 subjects)
On chromosome X but no X-linked pattern : male and females are affected equally
Haack2012 hypothesis: 
- somatic mosaicism in male (germline likely not viable)
    - female somatic + germline
    - severity based on when and where the mutation occurs in embryogenesis (like in Rett's syndrome)
    - in favor : 2 DNA traces of differents peaks 
- skewed X inactivation
    - in favor : skewed in 10/12 women with WDR45 mutation
# References
- [X] [@Aring_2021] review + physiopathology of WDR45 deficit
Design : in vitro model of neuronal fonction (SH-SY5Y neuroblastoma)
- modified iron uptake in cells
- possible link to increased iron uptake in neurons
- impaired ferritinophagy 
- mitochrondrial iron accumulation + altered mitochrondrial metabolism (possible link to neuronal cell death, neurodegenration)
- [ ] [@haylick2013] phenotype details of WDR45 mutation foudn in [@haack2012]
- [X] [@haack2012] first description of WDR45 in NBIA 
19 mutations, 20 subjects.
Mutation ok, phenotype TODO
[@Lee_iron_2021] c.974-1G>A  étude fibroblaste
[@lee_autophagic_2021] c.977-1G>A effet autophage fibroblaste
[@Ji_2021] autophagosome maturation into autolysosomes in neural cells
[@Kano_2020] revue 1 patiente

* Outline
** NBIA
Neurogeneration with brain iron accumulation = progressive
extrapyramidal with accumulation of iron in the brain on MRI, usually
basal ganglia.
- 85% have a genetic basis and most of these are due to 4
genes: /PKAN2/,/PLA2G6/, /C19orf12/, /WDR45/.
- In total, 9 genes are reported.
- Classification is based on genes.
- Clincal and MRI may orient to a specific gene (Table 19.2 in [cite:@haylick2018]).
- PKAN is half of the case and its estimated prevalence is 1/1 000 000 [cite:@gregory2002]
** Beta-propeller protein associated neurodegeneration
- Phenotype described in Gregory2002, Gregory2019.
- Genetic basis in Haack2012, with phenotype detailed in Haylick2013 (20 subjects)
- On chromosome X but no X-linked pattern : male and females are affected
equally
- Haack2012 hypothesis:
  - somatic mosaicism in male (germline likely not viable)
  - female somatic + germline
  - severity based on when and where the mutation occurs in embryogenesis (like in Rett's
syndrome)
  - in favor :
    - 2 DNA traces of differents peaks
    - skewed X inactivation
    - in favor : skewed in 10/12 women with WDR45 mutation
** References
- [ ] [cite:@Aring_2021] review + physiopathology of WDR45 deficit
  Design : in vitro model of neuronal fonction (SH-SY5Y neuroblastoma)
  - modified iron uptake in cells
  - possible link to increased iron uptake in neurons
  - impaired ferritinophagy
  - mitochrondrial iron accumulation + altered mitochrondrial metabolism (possible link to neuronal cell death, neurodegenration)
- [ ] [cite:@haylick2013] phenotype details of WDR45 mutation foudn in [cite:@haack2012]
- [ ] [cite:@haack2012] first description of WDR45 in NBIA 19 mutations, 20 subjects. Mutation ok, phenotype TODO
- [cite:@Lee_iron_2021] c.974-1G>A étude fibroblaste
- [cite:@lee_autophagic_2021] c.977-1G>A effet autophage fibroblaste
- [cite:@Ji_2021] autophagosome maturation into autolysosomes in neural cells
- [cite:@Kano_2020] revue 1 patiente