Genotype-phenotype correlations and expansion of the molecular spectrum of AP4M1-related hereditary spastic paraplegia.
Τίτλος | Genotype-phenotype correlations and expansion of the molecular spectrum of AP4M1-related hereditary spastic paraplegia. |
Publication Type | Journal Article |
Year of Publication | 2017 |
Authors | Bettencourt, C., Salpietro V., Efthymiou S., Chelban V., Hughes D., Pittman A. M., Federoff M., Bourinaris T., Spilioti M., Deretzi G., Kalantzakou T., Houlden H., Singleton A. B., & Xiromerisiou G. |
Journal | Orphanet J Rare Dis |
Volume | 12 |
Issue | 1 |
Pagination | 172 |
Date Published | 2017 11 02 |
ISSN | 1750-1172 |
Λέξεις κλειδιά | Basic Helix-Loop-Helix Leucine Zipper Transcription Factors, Female, Genetic Association Studies, Humans, Male, Mutation, Pedigree, Spastic Paraplegia, Hereditary |
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. |
DOI | 10.1186/s13023-017-0721-2 |
Alternate Journal | Orphanet J Rare Dis |
PubMed ID | 29096665 |
PubMed Central ID | PMC5669016 |
Grant List | / / Wellcome Trust / United Kingdom Z01 AG000957 / AG / NIA NIH HHS / United States |