AP4 deficiency: A novel form of neurodegeneration with brain iron accumulation?

Neurology. Genetics
Agathe RoubertieGuy Lenaers

Abstract

To describe the clinico-radiological phenotype of 3 patients harboring a homozygous novel AP4M1 pathogenic mutation. The 3 patients from an inbred family who exhibited early-onset developmental delay, tetraparesis, juvenile motor function deterioration, and intellectual deficiency were investigated by magnetic brain imaging using T1-weighted, T2-weighted, T2*-weighted, fluid-attenuated inversion recovery, susceptibility weighted imaging (SWI) sequences. Whole-exome sequencing was performed on the 3 patients. In the 3 patients, brain imaging identified the same pattern of bilateral SWI hyposignal of the globus pallidus, concordant with iron accumulation. A novel homozygous nonsense mutation was identified in AP4M1, segregating with the disease and leading to truncation of half of the adap domain of the protein. Our results suggest that AP4M1 represents a new candidate gene that should be considered in the neurodegeneration with brain iron accumulation (NBIA) spectrum of disorders and highlight the intersections between hereditary spastic paraplegia and NBIA clinical presentations.

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Citations

May 31, 2018·Current Opinion in Neurology·Livia ParodiAlexandra Durr
Dec 5, 2019·Brain : a Journal of Neurology·Hugo Morales-BriceñoVictor S C Fung
Jul 14, 2020·Current Opinion in Neurology·Stéphane LehéricyFanny Mochel
Oct 22, 2020·Biochemical Society Transactions·Rafael MatteraJuan S Bonifacino
Feb 26, 2021·Brain Communications·Shekeeb S MohammadUNKNOWN Basal Ganglia MRI Study Group
Mar 18, 2021·Zhurnal nevrologii i psikhiatrii imeni S.S. Korsakova·G E RudenskayaO P Ryzhkova
Apr 23, 2021·Neurological Sciences : Official Journal of the Italian Neurological Society and of the Italian Society of Clinical Neurophysiology·Anikha BelladBabylakshmi Muthusamy
Jun 5, 2021·The Canadian Journal of Neurological Sciences. Le Journal Canadien Des Sciences Neurologiques·Reza HajatiAfagh Alavi
Jul 9, 2021·Genetics in Medicine : Official Journal of the American College of Medical Genetics·Mehdi BenkiraneMichel Koenig
Sep 22, 2021·Neurology·Darius Ebrahimi-FakhariUNKNOWN International AP-4-HSP Registry and Natural History Study

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