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

Lookup NU author(s): Professor Rita Horvath



This work is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License (CC BY-NC-ND).


Copyright © 2018 The Author(s). Objective: To describe the clinico-radiological phenotype of 3 patients harboring a homozygous novel AP4M1 pathogenic mutation. Methods: The 3 patients from an inbred family who exhibited early-onset developmental delay, tetra-paresis, 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. Results: 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. Conclusions: 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.

Publication metadata

Author(s): Roubertie A, Hieu N, Roux C-J, Leboucq N, Manes G, Charif M, Echenne B, Goizet C, Guissart C, Meyer P, Marelli C, Rivier F, Burglen L, Horvath R, Hamel CP, Lenaers G

Publication type: Article

Publication status: Published

Journal: Neurology: Genetics

Year: 2018

Volume: 4

Issue: 1

Print publication date: 10/02/2018

Online publication date: 24/01/2018

Acceptance date: 10/12/2017

Date deposited: 02/07/2018

ISSN (electronic): 2376-7839

Publisher: Lippincott Williams and Wilkins


DOI: 10.1212/NXG.0000000000000217


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