ArticleAmerican journal of medical genetics. Part A2010
Somatic mosaicism in Menkes disease suggests choroid plexus-mediated copper transport to the developing brain.
Article in American journal of medical genetics. Part A, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 24 papers, 1 of them a synthesis that pooled it.
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Who cites it
24 citing papers in PubMed, 1 synthesis or guideline pooled it, 41 citations in OpenAlex.
- The copper radioisotopes: a systematic review with special interest to 64Cu.BioMed research international · 2014Pooled it
- Mammalian copper homeostasis: physiological roles and molecular mechanisms.Physiological reviews · 2025Review
- Atp7b-dependent choroid plexus dysfunction causes transient copper deficit and metabolic changes in the developing mouse brain.PLoS genetics · 2023Article
- Newly identified disorder of copper metabolism caused by variants in CTR1, a high-affinity copper transporter.Human molecular genetics · 2022Article
- Advances in visualization of copper in mammalian systems using X-ray fluorescence microscopy.Current opinion in chemical biology · 2020Review
- Emergence and Developmental Roles of the Cerebrospinal Fluid System.Developmental cell · 2020Review
- ATP7A Clinical Genetics Resource - A comprehensive clinically annotated database and resource for genetic variants in ATP7A gene.Computational and structural biotechnology journal · 2020Article
- Copper and the brain noradrenergic system.Journal of biological inorganic chemistry : JBIC : a publication of the Society of Biological Inorganic Chemistry · 2019Review
- Cerebrospinal Fluid-Directed rAAV9-rsATP7A Plus Subcutaneous Copper Histidinate Advance Survival and Outcomes in a Menkes Disease Mouse Model.Molecular therapy. Methods & clinical development · 2018Article
- Drosophila melanogaster Models of Metal-Related Human Diseases and Metal Toxicity.International journal of molecular sciences · 2017Review
- Autonomous requirements of the Menkes disease protein in the nervous system.American journal of physiology. Cell physiology · 2015Article
- Tandem Duplication of Exons 1-7 Neither Impairs ATP7A Expression Nor Causes a Menkes Disease Phenotype.JIMD reports · 2015Article
- Mottled Mice and Non-Mammalian Models of Menkes Disease.Frontiers in molecular neuroscience · 2015Review
- Regulation of copper transport crossing brain barrier systems by Cu-ATPases: effect of manganese exposure.Toxicological sciences : an official journal of the Society of Toxicology · 2014Article
- L-threo-dihydroxyphenylserine corrects neurochemical abnormalities in a Menkes disease mouse model.Annals of neurology · 2013Article
- Catecholamine metabolites affected by the copper-dependent enzyme dopamine-beta-hydroxylase provide sensitive biomarkers for early diagnosis of menkes disease and viral-mediated ATP7A gene therapy.Advances in pharmacology (San Diego, Calif.) · 2013Review
- Role of the P-Type ATPases, ATP7A and ATP7B in brain copper homeostasis.Frontiers in aging neuroscience · 2013Article
- Links between copper and cholesterol in Alzheimer's disease.Frontiers in physiology · 2013Article
- Maternofetal and neonatal copper requirements revealed by enterocyte-specific deletion of the Menkes disease protein.American journal of physiology. Gastrointestinal and liver physiology · 2012Article
- In utero copper treatment for Menkes disease associated with a severe ATP7A mutation.Molecular genetics and metabolism · 2012Article
Corrections and comments
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Authors and funding
4 authors at 3 institutions in 1 country.
Funding
Abstract
The primary mechanism of copper transport to the brain is unknown, although this process is drastically impaired in Menkes disease, an X-linked neurodevelopmental disorder caused by mutations in an evolutionarily conserved copper transporter, ATP7A. Potential central nervous system entry routes for copper include brain capillary endothelial cells that originate from mesodermal angioblasts and form the blood-brain barrier, and the choroid plexuses, which derive from embryonic ectoderm, and form the blood-cerebrospinal fluid barrier. We exploited a rare (and first reported) example of somatic mosaicism for an ATP7A mutation to shed light on questions about copper transport into the developing brain. In a 20-month-old Menkes disease patient evaluated before copper treatment, blood copper, and catecholamine concentrations were normal, whereas levels in cerebrospinal fluid were abnormal and consistent with his neurologically severe phenotype. We documented disparate levels of mosaicism for an ATP7A missense mutation, P1001L, in tissues derived from different embryonic origins; allele quantitation showed P1001L in approximately 27% of DNA samples from blood cells (mesoderm-derived) and 88% from cultured fibroblasts (ectoderm-derived). These findings imply that the P1001L mutation in the patient preceded formation of the three primary embryonic lineages at gastrulation, with the ectoderm layer ultimately harboring a higher percentage of mutation-bearing cells than mesoderm or endoderm. Since choroid plexus epithelia are derived from neuroectoderm, and brain capillary endothelial cells from mesodermal angioblasts, the clinical and biochemical findings in this infant support a critical role for the blood-CSF barrier (choroid plexus epithelia) in copper entry to the developing brain.
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