Title |
Genotype-phenotype correlations and expansion of the molecular spectrum of AP4M1-related hereditary spastic paraplegia
|
---|---|
Published in |
Orphanet Journal of Rare Diseases, November 2017
|
DOI | 10.1186/s13023-017-0721-2 |
Pubmed ID | |
Authors |
Conceição Bettencourt, Vincenzo Salpietro, Stephanie Efthymiou, Viorica Chelban, Deborah Hughes, Alan M. Pittman, Monica Federoff, Thomas Bourinaris, Martha Spilioti, Georgia Deretzi, Triantafyllia Kalantzakou, Henry Houlden, Andrew B. Singleton, Georgia Xiromerisiou |
Abstract |
Autosomal recessive hereditary spastic paraplegia (HSP) due to AP4M1 mutations is a very rare neurodevelopmental disorder reported for only a few patients. We investigated a Greek HSP family using whole exome sequencing (WES). 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. 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. |
X Demographics
Geographical breakdown
Country | Count | As % |
---|---|---|
United Kingdom | 1 | 33% |
United States | 1 | 33% |
Unknown | 1 | 33% |
Demographic breakdown
Type | Count | As % |
---|---|---|
Members of the public | 3 | 100% |
Mendeley readers
Geographical breakdown
Country | Count | As % |
---|---|---|
Unknown | 38 | 100% |
Demographic breakdown
Readers by professional status | Count | As % |
---|---|---|
Student > Ph. D. Student | 6 | 16% |
Researcher | 5 | 13% |
Other | 3 | 8% |
Student > Doctoral Student | 3 | 8% |
Student > Postgraduate | 2 | 5% |
Other | 6 | 16% |
Unknown | 13 | 34% |
Readers by discipline | Count | As % |
---|---|---|
Medicine and Dentistry | 10 | 26% |
Neuroscience | 4 | 11% |
Social Sciences | 4 | 11% |
Biochemistry, Genetics and Molecular Biology | 3 | 8% |
Nursing and Health Professions | 2 | 5% |
Other | 2 | 5% |
Unknown | 13 | 34% |