ArticleOrphanet journal of rare diseases2018
Recessive mutations in ATP8A2 cause severe hypotonia, cognitive impairment, hyperkinetic movement disorders and progressive optic atrophy.
Article in Orphanet journal of rare diseases, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 25 papers, 2 of them syntheses that pooled it.
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Who cites it
25 citing papers in PubMed, 2 syntheses or guidelines pooled it, 45 citations in OpenAlex.
- Expanding the spectrum of ATP8A2 mutations: a new splicing variant and systematic review of CAMRQ4 syndrome.Molecular biology reports · 2025Pooled it
- Catching the Culprit: How Chorea May Signal an Inborn Error of Metabolism.Tremor and other hyperkinetic movements (New York, N.Y.) · 2023Pooled it
- Loss of Atp8a2 drives neurodegeneration through the dysregulation of spatiotemporal phosphatidylserine externalization in mature neurons.Cell death & disease · 2026Article
- Early-Onset Hyperkinetic Movement Disorders Define the Most Severe Presentation of the ATP8A2-Related Phenotypic Spectrum.International journal of developmental neuroscience : the official journal of the International Society for Developmental Neuroscience · 2026Article
- TDP-43 suppression of ATP8A2 cryptic splicing implicates phosphatidylserine-driven neuroinflammation in ALS/FTD.bioRxiv : the preprint server for biology · 2025Article
- A novel missense variant in the ATPase domain of ATP8A2 and review of phenotypic variability of ATP8A2-related disorders caused by missense changes.Neurogenetics · 2024Article
- Exploring the Genetic Landscape of Chorea in Infancy and Early Childhood: Implications for Diagnosis and Treatment.Current issues in molecular biology · 2024Review
- Functional and in silico analysis of ATP8A2 and other P4-ATPase variants associated with human genetic diseases.Disease models & mechanisms · 2024Article
- A novel missense variant in the ATPase domain of ATP8A2 and review of phenotypic variability ofmedRxiv : the preprint server for health sciences · 2024Article
- Flipping the script: Advances in understanding how and why P4-ATPases flip lipid across membranes.Biochimica et biophysica acta. Molecular cell research · 2024Review
- Article
- Regulation of phospholipid distribution in the lipid bilayer by flippases and scramblases.Nature reviews. Molecular cell biology · 2023Review
- ATP9A deficiency causes ADHD and aberrant endosomal recycling via modulating RAB5 and RAB11 activity.Molecular psychiatry · 2023Article
- Physiological and Pathological Functions of TMEM30A: An Essential Subunit of P4-ATPase Phospholipid Flippases.Journal of lipids · 2023Review
- Lipid Transport byInfection and immunity · 2022Article
- Biallelic truncation variants in ATP9A are associated with a novel autosomal recessive neurodevelopmental disorder.NPJ genomic medicine · 2021Article
- Phospholipid-flippase chaperone CDC50A is required for synapse maintenance by regulating phosphatidylserine exposure.The EMBO journal · 2021Article
- A vertebrate adaptive radiation is assembled from an ancient and disjunct spatiotemporal landscape.Proceedings of the National Academy of Sciences of the United States of America · 2021Article
- Genome-wide association study for postweaning weight traits in Lori-Bakhtiari sheep.Tropical animal health and production · 2021Article
- A novel homozygous variant in an Iranian pedigree with cerebellar ataxia, mental retardation, and dysequilibrium syndrome type 4.Journal of clinical laboratory analysis · 2020Article
Corrections and comments
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Authors and funding
30 authors at 16 institutions in 9 countries.
Funding
Abstract
backgroundATP8A2 mutations have recently been described in several patients with severe, early-onset hypotonia and cognitive impairment. The aim of our study was to characterize the clinical phenotype of patients with ATP8A2 mutations.
methodsAn observational study was conducted at multiple diagnostic centres. Clinical data is presented from 9 unreported and 2 previously reported patients with ATP8A2 mutations. We compare their features with 3 additional patients that have been previously reported in the medical literature.
resultsEleven patients with biallelic ATP8A2 mutations were identified, with a mean age of 9.4 years (range 2.5-28 years). All patients with ATP8A2 mutations (100%) demonstrated developmental delay, severe hypotonia and movement disorders, specifically chorea or choreoathetosis (100%), dystonia (27%) and facial dyskinesia (18%). Optic atrophy was observed in 78% of patients for whom funduscopic examination was performed. Symptom onset in all (100%) was noted before 6 months of age, with 70% having symptoms noted at birth. Feeding difficulties were common (91%) although most patients were able to tolerate pureed or thickened feeds, and 3 patients required gastrostomy tube insertion. MRI of the brain was normal in 50% of the patients. A smaller proportion was noted to have mild cortical atrophy (30%), delayed myelination (20%) and/or hypoplastic optic nerves (20%). Functional studies were performed on differentiated induced pluripotent cells from one child, which confirmed a decrease in ATP8A2 expression compared to control cells.
conclusionsATP8A2 gene mutations have emerged as the cause of a novel neurological phenotype characterized by global developmental delays, severe hypotonia and hyperkinetic movement disorders, the latter being an important distinguishing feature. Optic atrophy is common and may only become apparent in the first few years of life, necessitating repeat ophthalmologic evaluation in older children. Early recognition of the cardinal features of this condition will facilitate diagnosis of this complex neurologic disorder.
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