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Potential central nervous system entry routes for copper include brain capillary endothelial cells that originate from mesodermal angioblasts and form the blood\u2013brain barrier, and the choroid plexuses, which derive from embryonic ectoderm, and form the blood\u2013cerebrospinal 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\u2010month\u2010old 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\u2010derived) and 88% from cultured fibroblasts (ectoderm\u2010derived). 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\u2010bearing 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\u2013CSF barrier (choroid plexus epithelia) in copper entry to the developing brain. \u00a9 2010 Wiley\u2010Liss, Inc.<\/jats:p>","DOI":"10.1002\/ajmg.a.33632","type":"journal-article","created":{"date-parts":[[2010,8,30]],"date-time":"2010-08-30T17:51:57Z","timestamp":1283190717000},"page":"2529-2534","source":"Crossref","is-referenced-by-count":37,"title":["Somatic mosaicism in Menkes disease suggests choroid plexus\u2010mediated copper transport to the developing brain"],"prefix":"10.1002","volume":"152A","author":[{"given":"Anthony","family":"Donsante","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Paul","family":"Johnson","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Laura A.","family":"Jansen","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Stephen G.","family":"Kaler","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2010,8,26]]},"reference":[{"key":"e_1_2_6_2_1","doi-asserted-by":"publisher","DOI":"10.1172\/JCI117120"},{"key":"e_1_2_6_3_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuroimage.2004.03.031"},{"key":"e_1_2_6_4_1","doi-asserted-by":"publisher","DOI":"10.1007\/s10534-006-9055-6"},{"key":"e_1_2_6_5_1","doi-asserted-by":"publisher","DOI":"10.1038\/ng1228"},{"key":"e_1_2_6_6_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0003114"},{"key":"e_1_2_6_7_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1399-0004.1982.tb01846.x"},{"key":"e_1_2_6_8_1","first-page":"153","article-title":"Embryonic and fetal development of structures associated with the cerebrospinal fluid in man and other species. 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