Please use this identifier to cite or link to this item:
https://hdl.handle.net/2445/182762
Title: | Biallelic PI4KA variants cause a novel neurodevelopmental syndrome with hypomyelinating leukodystrophy |
Author: | Verdura, Edgard Rodríguez Palmero, Agustí Vélez Santamaría, Valentina Planas Serra, Laura Calle, Irene de la Raspall Chaure, Miquel Roubertie, Agathe Benkirane, Mehdi Saettini, Francesco Pavinato, Lisa Mandrile, Giorgia O’leary, Melanie O’heir, Emily Barredo, Estibaliz Chacón, Almudena Michaud, Vincent Goizet, Cyril Ruiz, Montserrat Schlüter, Agatha Rouvet, Isabelle Sala Coromina, Júlia Fossati, Chiara Iascone, Maria Canonico, Francesco Marcé Grau, Anna Souza, Precilla de Adams, David Casasnovas Pons, Carlos Rehm, Heidi L. Mefford, Heather C. González Gutiérrez-Solana, Luis Brusco, Alfredo Koenig, Michel Macaya, Alfons Pujol, Aurora |
Keywords: | Malalties del sistema nerviós central Malalties hereditàries Central nervous system diseases Genetic disorders |
Issue Date: | 20-Aug-2021 |
Publisher: | Oxford University Press (OUP) |
Abstract: | Phosphoinositides are lipids that play a critical role in processes such as cellular signalling, ion channel activity and membrane trafficking. When mutated, several genes that encode proteins that participate in the metabolism of these lipids give rise to neurological or developmental phenotypes. PI4KA is a phosphoinositide kinase that is highly expressed in the brain and is essential for life. Here we used whole exome or genome sequencing to identify 10 unrelated patients harbouring biallelic variants in PI4KA that caused a spectrum of conditions ranging from severe global neurodevelopmental delay with hypomyelination and developmental brain abnormalities to pure spastic paraplegia. Some patients presented immunological deficits or genito-urinary abnormalities. Functional analyses by western blotting and immunofluorescence showed decreased PI4KA levels in the patients' fibroblasts. Immunofluorescence and targeted lipidomics indicated that PI4KA activity was diminished in fibroblasts and peripheral blood mononuclear cells. In conclusion, we report a novel severe metabolic disorder caused by PI4KA malfunction, highlighting the importance of phosphoinositide signalling in human brain development and the myelin sheath. |
Note: | Reproducció del document publicat a: https://doi.org/10.1093/brain/awab124 |
It is part of: | Brain, 2021, vol 144, num 9, p. 2659-2669 |
URI: | https://hdl.handle.net/2445/182762 |
Related resource: | https://doi.org/10.1093/brain/awab124 |
ISSN: | 1460-2156 |
Appears in Collections: | Articles publicats en revistes (Ciències Clíniques) Articles publicats en revistes (Institut d'lnvestigació Biomèdica de Bellvitge (IDIBELL)) |
Files in This Item:
File | Description | Size | Format | |
---|---|---|---|---|
awab124.pdf | 1.51 MB | Adobe PDF | View/Open |
This item is licensed under a
Creative Commons License