ArticleAmerican journal of human genetics2009
Mutation in the AP4M1 gene provides a model for neuroaxonal injury in cerebral palsy.
Article in American journal of human genetics, 2009. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 100 papers, 1 of them a synthesis that pooled it.
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100 citing papers in PubMed, 1 synthesis or guideline pooled it, 172 citations in OpenAlex.
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- Identifying SHROOM4 as a novel X-linked susceptibility gene for cerebral palsy in Chinese males.BMC pediatrics · 2026Article
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- EIPR1 variants cause a neurodevelopmental disorder with endolysosomal and dense core vesicle defects.Brain : a journal of neurology · 2026Article
- The Golgi apparatus: adaptations to neuronal shape and functions.The EMBO journal · 2026Review
- AP2M1 Is a Candidate Gene for Microcephaly and Intellectual Disability in 3q27.1 Deletions.American journal of medical genetics. Part A · 2025Article
- A Case of Hereditary Spastic Paraplegia Type 50 With a Novel AP4M1 Variant and a Brief Review of the Literature.Clinical case reports · 2025Article
- Burden of pathogenetic and likely pathogenetic variants in SPG7, SPG11 and AP4 genes in Amyotrophic Lateral Sclerosis. A case-control study.Journal of neurology · 2025Article
- Strabismus in Genetic Syndromes: A Review.Clinical & experimental ophthalmology · 2025Review
- Neurodevelopmental Implications Underpinning Hereditary Spastic Paraplegia.CNS neuroscience & therapeutics · 2025Review
- AP2A2 mutation and defective endocytosis in a Malian family with hereditary spastic paraplegia.Neurobiology of disease · 2024Article
- Biallelic BORCS8 variants cause an infantile-onset neurodegenerative disorder with altered lysosome dynamics.Brain : a journal of neurology · 2024Article
- Exome sequencing reveals genetic heterogeneity and clinically actionable findings in children with cerebral palsy.Nature medicine · 2024Article
- Review
- Single nucleotide polymorphisms conferring susceptibility to leukemia and oral mucositis: a multi-center pilot study of patients prior to conditioning therapy for hematopoietic cell transplant.Supportive care in cancer : official journal of the Multinational Association of Supportive Care in Cancer · 2024Article
- The Reelin receptor ApoER2 is a cargo for the adaptor protein complex AP-4: Implications for Hereditary Spastic Paraplegia.Progress in neurobiology · 2024Article
- Pathological mutations reveal the key role of the cytosolic iRhom2 N-terminus for phosphorylation-independent 14-3-3 interaction and ADAM17 binding, stability, and activity.Cellular and molecular life sciences : CMLS · 2024Article
- Article
- Paving a way to treat spastic paraplegia 50.The Journal of clinical investigation · 2023Article
- Intrathecal AAV9/AP4M1 gene therapy for hereditary spastic paraplegia 50 shows safety and efficacy in preclinical studies.The Journal of clinical investigation · 2023Article
40 more citing papers are in PubMed but not listed here.
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Authors and funding
21 authors at 2 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Cerebral palsy due to perinatal injury to cerebral white matter is usually not caused by genetic mutations, but by ischemia and/or inflammation. Here, we describe an autosomal-recessive type of tetraplegic cerebral palsy with mental retardation, reduction of cerebral white matter, and atrophy of the cerebellum in an inbred sibship. The phenotype was recorded and evolution followed for over 20 years. Brain lesions were studied by diffusion tensor MR tractography. Homozygosity mapping with SNPs was performed for identification of the chromosomal locus for the disease. In the 14 Mb candidate region on chromosome 7q22, RNA expression profiling was used for selecting among the 203 genes in the area. In postmortem brain tissue available from one patient, histology and immunohistochemistry were performed. Disease course and imaging were mostly reminiscent of hypoxic-ischemic tetraplegic cerebral palsy, with neuroaxonal degeneration and white matter loss. In all five patients, a donor splice site pathogenic mutation in intron 14 of the AP4M1 gene (c.1137+1G-->T), was identified. AP4M1, encoding for the mu subunit of the adaptor protein complex-4, is involved in intracellular trafficking of glutamate receptors. Aberrant GluRdelta2 glutamate receptor localization and dendritic spine morphology were observed in the postmortem brain specimen. This disease entity, which we refer to as congenital spastic tetraplegia (CST), is therefore a genetic model for congenital cerebral palsy with evidence for neuroaxonal damage and glutamate receptor abnormality, mimicking perinatally acquired hypoxic-ischemic white matter injury.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.