Periventricular small cystic lesions in a patient with Coffin-Lowry syndrome who exhibited a novel mutation in the RPS6KA3 gene

Miyata, Yohane; Saida, Ken; Kumada, Satoko; Miyake, Noriko; Mashimo, Hideaki; Nishida, Yuya; Shirai, Ikuko; Kurihara, Eiji; Nakata, Yasuhiro; Matsumoto, Naomichi

doi:10.1016/j.braindev.2018.03.012

Cited by 4 publications

(1 citation statement)

References 10 publications

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“…26,27 Brain MRI can show cerebral atrophy, hypoplasia of the corpus callosum or the cerebellar vermis, ventricular dilatation or asymmetry, dilatation of the Virchow–Robin spaces leading to periventricular white matter cystic lesions, and constricted foramen magnum. 28–31…”

Section: Discussionmentioning

confidence: 99%

Deleterious mutations in ALDH1L2 suggest a novel cause for neuro-ichthyotic syndrome

et al. 2019

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Neuro-ichthyotic syndromes are a group of rare genetic diseases mainly associated with perturbations in lipid metabolism, intracellular vesicle trafficking, or glycoprotein synthesis. Here, we report a patient with a neuro-ichthyotic syndrome associated with deleterious mutations in the ALDH1L2 (aldehyde dehydrogenase 1 family member L2) gene encoding for mitochondrial 10-formyltetrahydrofolate dehydrogenase. Using fibroblast culture established from the ALDH1L2-deficient patient, we demonstrated that the enzyme loss impaired mitochondrial function affecting both mitochondrial morphology and the pool of metabolites relevant to β-oxidation of fatty acids. Cells lacking the enzyme had distorted mitochondria, accumulated acylcarnitine derivatives and Krebs cycle intermediates, and had lower ATP and increased ADP/AMP indicative of a low energy index. Re-expression of functional ALDH1L2 enzyme in deficient cells restored the mitochondrial morphology and the metabolic profile of fibroblasts from healthy individuals. Our study underscores the role of ALDH1L2 in the maintenance of mitochondrial integrity and energy balance of the cell, and suggests the loss of the enzyme as the cause of neuro-cutaneous disease.

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