Objective: Biallelic mutations in the AP5Z1 gene encoding the AP-5 ζ subunit have been described in a small number of patients with hereditary spastic paraplegia (HSP) (SPG48); we sought to define genotype-phenotype correlations in patients with homozygous or compound heterozygous sequence variants predicted to be deleterious.
Methods: We performed clinical, radiologic, and pathologic studies in 6 patients with biallelic mutations in AP5Z1.
Results: In 4 of the 6 patients, there was complete loss of AP-5 ζ protein. Clinical features encompassed not only prominent spastic paraparesis but also sensory and motor neuropathy, ataxia, dystonia, myoclonus, and parkinsonism. Skin fibroblasts from affected patients tested positive for periodic acid Schiff and autofluorescent storage material, while electron microscopic analysis demonstrated lamellar storage material consistent with abnormal storage of lysosomal material.
Conclusions: Our findings expand the spectrum of AP5Z1-associated neurodegenerative disorders and point to clinical and pathophysiologic overlap between autosomal recessive forms of HSP and lysosomal storage disorders.
Download full-text PDF |
Source |
|---|---|
| http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5001803 | PMC |
| http://dx.doi.org/10.1212/NXG.0000000000000098 | DOI Listing |
Publication Analysis
Top Keywords
Similar Publications
High-density multielectrode arrays bring cellular resolution to neuronal activity and network analyses of corticospinal motor neurons.
Sci Rep
January 2025
Department of Neurology, Feinberg School of Medicine, Northwestern University, 303 E. Chicago Ave, Chicago, IL, 60611, USA.
Corticospinal motor neurons (CSMN), located in the motor cortex of the brain, are one of the key components of the motor neuron circuitry. They are in part responsible for the initiation and modulation of voluntary movement, and their degeneration is the hallmark for numerous diseases, such as amyotrophic lateral sclerosis (ALS), hereditary spastic paraplegia, and primary lateral sclerosis. Cortical hyperexcitation followed by in-excitability suggests the early involvement of cortical dysfunction in ALS pathology.
View Article and Find Full Text PDFBasic Science and Pathogenesis.
Alzheimers Dement
December 2024
University of Guadalajara, Guadalajara, JA, Mexico.
Background: The ways in which diverse genetic variants interact to affect the phenotype of AD is poorly understood. The relatively consistent phenotype associated with specific mutations causing autosomal dominant AD (ADAD) provides the opportunity to study how other genetic variants contribute to disease manifestations.
Method: We performed an in-depth case study of a patient with the A431E PSEN1 mutation who had onset of progressive spastic paraplegia at age 20.
Basic Science and Pathogenesis.
Alzheimers Dement
December 2024
University of Perugia, Perugia, Italy.
Background: We researched the occurrence, neuropathology, and clinical features of spastic paraplegia (SP) associated to dementia in presenilin 1 (PSEN1) Italian patients related to familial Alzheimer's disease (AD).
Methods: We carried out whole exome sequencing in 33 familial AD probands with hereditary spastic paraplegia (HSP) that resulted negative for the identification of pathogenetic variants in known HSP genes. One patient was identified with a DNA variant in PSEN1, and bioinformatic analysis was conducted to characterize its pathogenetic nature.
Endovascular single-branched stent graft to treat complicated type B aortic dissection involving aortic arch anomalies.
Eur J Med Res
December 2024
Department of Peripheral Vascular Diseases, The First Affiliated Hospital of Xi'an Jiaotong University, No. 277, Yanta West Road, Xi'an, Shaanxi, China.
Background: The optimal treatment of complicated type B aortic dissection (cTBAD) involving arch anomalies remain unclear.
Methods: We consecutively enrolled patients with cTBAD involving arch anomalies who underwent endovascular repair using a single-branched stent graft (SBSG) at our medical center between January 2020 and January 2023. The demographics, clinical manifestation, operation detail, and follow-up outcomes of these patients were retrospectively collected and analyzed.
Expanding molecular and clinical spectrum of CPT1C-associated hereditary spastic paraplegia (SPG73)-a case series.
Ann Clin Transl Neurol
December 2024
Department of Neurology, Movement Disorders Program, Boston Children's Hospital, Harvard Medical School, Boston, Massachusetts, USA.
Autosomal-dominant variants in the CPT1C gene have been associated with hereditary spastic paraplegia type 73 (SPG73), which typically presents with slowly progressive lower limb weakness and spasticity and is therefore considered a pure form of hereditary spastic paraplegia. However, we report two unrelated males with novel CPT1C variants (NM_001199753.2: patient 1: c.
View Article and Find Full Text PDFWant AI Summaries of new PubMed Abstracts delivered to your In-box?
Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!