Bettencourt, C;
Salpietro, V;
Efthymiou, S;
Chelban, V;
Hughes, D;
Pittman, AM;
Federoff, M;
... Xiromerisiou, G; + view all
(2017)
Genotype-phenotype correlations and expansion of the molecular spectrum of AP4M1-related hereditary spastic paraplegia.
Orphanet Journal of Rare Diseases
, 12
, Article 172. 10.1186/s13023-017-0721-2.
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Abstract
BACKGROUND: Autosomal recessive hereditary spastic paraplegia (HSP) due to AP4M1 mutations is a very rare neurodevelopmental disorder reported for only a few patients. METHODS: We investigated a Greek HSP family using whole exome sequencing (WES). RESULTS: A novel AP4M1A frameshift insertion, and a very rare missense variant were identified in all three affected siblings in the compound heterozygous state (p.V174fs and p.C319R); the unaffected parents were carriers of only one variant. Patients were affected with a combination of: (a) febrile seizures with onset in the first year of life (followed by epileptic non-febrile seizures); (b) distinctive facial appearance (e.g., coarse features, bulbous nose and hypomimia); (c) developmental delay and intellectual disability; (d) early-onset spastic weakness of the lower limbs; and (e) cerebellar hypoplasia/atrophy on brain MRI. CONCLUSIONS: We review genotype-phenotype correlations and discuss clinical overlaps between different AP4-related diseases. The AP4M1 belongs to a complex that mediates vesicle trafficking of glutamate receptors, being likely involved in brain development and neurotransmission.
| Type: | Article |
|---|---|
| Title: | Genotype-phenotype correlations and expansion of the molecular spectrum of AP4M1-related hereditary spastic paraplegia |
| Open access status: | An open access version is available from UCL Discovery |
| DOI: | 10.1186/s13023-017-0721-2 |
| Publisher version: | http://doi.org/10.1186/s13023-017-0721-2 |
| Language: | English |
| Additional information: | © The Author(s). 2017. This article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated. |
| Keywords: | Science & Technology, Life Sciences & Biomedicine, Genetics & Heredity, Medicine, Research & Experimental, Research & Experimental Medicine, Whole exome sequencing, AP4 complex, Epilepsy, Hereditary spastic paraplegia, Cerebellar hypoplasia, DEVELOPMENTAL-DISABILITIES, AUTOSOMAL-DOMINANT, MUTATION, DISORDERS, DISEASE, VARIANTS, FEATURES, GENES, AP4M1 |
| UCL classification: | UCL UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Brain Sciences UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Brain Sciences > UCL Queen Square Institute of Neurology UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Brain Sciences > UCL Queen Square Institute of Neurology > Department of Neuromuscular Diseases UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Brain Sciences > UCL Queen Square Institute of Neurology > Neurodegenerative Diseases |
| URI: | https://discovery-pp.ucl.ac.uk/id/eprint/10037502 |
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