P5CS expression study in a new family with ALDH18A1‐associated hereditary spastic paraplegia SPG9

@article{Magini2019P5CSES,
  title={P5CS expression study in a new family with ALDH18A1‐associated hereditary spastic paraplegia SPG9},
  author={Pamela Magini and Clara Marco-Mar{\'i}n and Juan M Escamilla-Honrubia and Diego Martinelli and Carlo Dionisi-Vici and Francesca Faravelli and Francesca Forzano and Marco Seri and Vicente Rubio and Emanuele Panza},
  journal={Annals of Clinical and Translational Neurology},
  year={2019},
  volume={6},
  pages={1533 - 1540}
}
In 2015–2016, we and others reported ALDH18A1 mutations causing dominant (SPG9A) or recessive (SPG9B) spastic paraplegia. In vitro production of the ALDH18A1 product, Δ1‐pyrroline‐5‐carboxylate synthetase (P5CS), appeared necessary for cracking SPG9 disease‐causing mechanisms. We now describe a baculovirus–insect cell system that yields mgs of pure human P5CS and that has proven highly valuable with two novel P5CS mutations reported here in new SPG9B patients. We conclude that both mutations… 
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Novel Compound Missense and Intronic Splicing Mutation in ALDH18A1 Causes Autosomal Recessive Spastic Paraplegia
TLDR
The genetic and clinical spectrum of SPG9B caused by ALDH18A1 mutation is expanded, and new genetic variants to facilitate future diagnoses are defined to demonstrate the highly informative value of splicing mutation prediction in the characterization of disease-related intronic variants.
Δ1‐Pyrroline‐5‐carboxylate synthetase deficiency: An emergent multifaceted urea cycle‐related disorder
TLDR
It is concluded that two neurocutaneous syndromes (recessive and dominant cutis laxa 3, abbreviated ARCL3A and ADCL3, respectively) and two SPG9 syndrome are caused by essentially different spectra of ALDH18A1 mutations, which represent a continuum of increasing severity.
Expanding the Spectrum of Neurological Manifestations in Cutis Laxa, Autosomal Recessive, Type IIIA.
TLDR
A 13-month-old patient with cutis laxa, autosomal recessive, type IIIA, with an extremely severe phenotype is described, including novel neurological findings, which enlarges the neurological spectrum associated with this syndrome.
Structural basis of dynamic P5CS filaments
TLDR
Cryo-electron microscopy reveals that filamentation is crucial for the coordination between the GK and GPR domains, providing a structural basis for the catalytic function of P5CS filaments.
The Multifaceted Roles of Proline in Cell Behavior
TLDR
It is highlighted how proline metabolism impacts beneficial tissue regeneration, but also contributes to the progression of devastating pathologies such as fibrosis and metastatic cancer.
The Janus-like role of proline metabolism in cancer
TLDR
A comprehensive review of proline metabolism in cancer is provided; the experimental evidence that links prolines metabolism with the different aspects of cancer progression and the potential mechanisms involved are collated.
Tremor as an early sign of hereditary spastic paraplegia due to mutations in ALDH18A1
Structural basis of dynamic P 5 CS filaments 1 2

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