In developing mammalian (mouse) brain, Reelin (Reln) is secreted by the Cajal-Retzius (CR) neurons in the marginal zone, binds apolipoprotein E receptor 2 (ApoER2) and very low density lipoprotein receptor (Vldlr), and induces the phosphorylation of the downstream cytoplasmic molecule disabled-1 (Dab1) in cortical plate neurons. Although this is a well-characterized signaling pathway in mice, it has not been well defined in human brain. In this paper we examined the expression of RELN, APOER2, VLDLR, and DAB1 in the developing human brain by RT-PCR. We further determined the cellular expression of the proteins RELN and DAB1 in 50 human brains ranging in age from 10 gestational weeks (GW) to 62 years using immunochemistry. We found that the pattern of expression of RELN and DAB1 in the human brain is not identical to that observed in the mouse brain. In particular, we report the novel finding that human DAB1 and RELN are coexpressed in CR neurons during cortical development and in cortical pyramidal neurons after neuronal migration is complete. Thus, in the human brain, the whole RELN signaling pathway is present within selected populations of cortical neurons throughout life. We speculate that RELN and DAB1 coexpression in these neurons is necessary for both normal cortical development and mature function.

Objective: To assess alterations in brain metabolites of patients with Pelizaeus–Merzbacher disease (PMD) with the proteolipid protein gene 1 (PLP1) duplications using quantitative proton MRS. Methods: Five unrelated male Japanese patients with PMD with PLP1 duplications were analyzed using automated proton brain examination with the point resolved spectroscopy technique (repetition and echo time of 5,000 and 30 msec). Localized spectra in the posterior portion of the centrum semiovale were acquired, and absolute metabolite concentrations were calculated using the LCModel. Results: Absolute concentrations of N-acetylaspartate (NAA), creatine (Cr), and myoinositol (MI) were increased by 16% (p < 0.01), 43% (p < 0.001), and 31% (p < 0.01) in patients with PMD as compared with age-matched controls. There was no statistical difference in choline concentration. Conclusion: The increased concentration of NAA, which could not be detected by previous relative quantitation methods, suggests two possibilities: axonal involvement secondary to dysmyelination, or increased cell population of oligodendrocyte progenitors. Elevated Cr and MI concentrations may reflect the reactive astrocytic gliosis. Our study thus emphasizes the importance of absolute quantitation of metabolites to investigate the disease mechanism of the dysmyelinating disorders of the CNS.

BACKGROUND AND PURPOSEPelizaeus-Merzbacher's disease (PMD) is caused by mutations in the proteolipid protein (PLP) gene. Recent studies have shown that an increased PLP dosage, resulting from total duplication of the PLP gene, invariably causes the classic form of PMD. The purpose of this study was to compare the MR findings of PMD attributable to PLP duplication with those of PMD arising from a missense mutation.METHODSSeven patients with PMD, three with a PLP missense mutation in either exon 2 or 5 (patients 1-3), and four with PLP duplication (patient 4 having larger PLP duplication than patients 5-7) were clinically classified as having either the classic or connatal form of PMD. Cerebral MR images were obtained to analyze the presence of myelination and T1 and T2 shortening in the deep gray matter. Multiple MR studies were performed in six of the seven patients to analyze longitudinal changes.RESULTSFour patients (patients 1-4) were classified as having connatal PMD, whereas the other three (patients 5-7) were classified as having classic PMD. Myelination in the cerebral corticospinal tract, optic radiation, and corpus callosum was observed in three cases of classic PMD with PLP duplication. In patient 4, myelination extended to the internal capsule, corona radiata, and centrum semiovale over a 3-year period. No myelination was observed in three PMD cases with a PLP point mutation. T2 shortening in the deep gray matter was recognized in all patients with PMD.CONCLUSIONThe presence of myelination in the cerebral corticospinal tract with diffuse white matter hypomyelination on MR images could be a marker for PMD with PLP duplication. It is suggested that progression of myelination may be present in connatal PMD with large PLP duplication.

Human MutationVolume 6, Issue 2 p. 186-187 Mutation in Brief New point mutation (R301X) of the α-galactosidase a gene causing fabry disease Chiaki Kawanishi, Corresponding Author Chiaki Kawanishi Department of Psychiatry, Yokohama City University School of Medicine, Yokohama 236, Japan; Fax: 81-45-783-2540Department of Psychiatry, Yokohama City University School of Medicine, Yokohama 236, Japan; Fax: 81-45-783-2540Search for more papers by this authorHitoshi Osaka, Hitoshi Osaka Department of Pediatrics, Yokohama City University School of Medicine, Yokohama 236, Japan; Fax: 81-45-783-2540Search for more papers by this authorKen Inoue, Ken Inoue Department of Psychiatry, Yokohama City University School of Medicine, Yokohama 236, Japan; Fax: 81-45-783-2540Search for more papers by this authorHideki Onishi, Hideki Onishi Department of Psychiatry, Yokohama City University School of Medicine, Yokohama 236, Japan; Fax: 81-45-783-2540Search for more papers by this authorYoshiteru Yamada, Yoshiteru Yamada Department of Psychiatry, Yokohama City University School of Medicine, Yokohama 236, Japan; Fax: 81-45-783-2540Search for more papers by this authorNaoya Sugiyama, Naoya Sugiyama Department of Psychiatry, Yokohama City University School of Medicine, Yokohama 236, Japan; Fax: 81-45-783-2540Search for more papers by this authorKyoko Suzuki, Kyoko Suzuki Department of Psychiatry, Yokohama City University School of Medicine, Yokohama 236, Japan; Fax: 81-45-783-2540Search for more papers by this authorTokiji Hanihara, Tokiji Hanihara Department of Psychiatry, Yokohama City University School of Medicine, Yokohama 236, Japan; Fax: 81-45-783-2540Search for more papers by this authorTomohiro Miyagawa, Tomohiro Miyagawa Department of Psychiatry, Yokohama City University School of Medicine, Yokohama 236, Japan; Fax: 81-45-783-2540Search for more papers by this authorSeiji Kimura, Seiji Kimura Department of Pediatrics, Yokohama City University School of Medicine, Yokohama 236, Japan; Fax: 81-45-783-2540 Department of Bacteriology, Yokohama City University School of Medicine, Yokohama 236, Japan; Fax: 81-45-783-2540Search for more papers by this authorSusumu Kawamoto, Susumu Kawamoto Department of Psychiatry, Yokohama City University School of Medicine, Yokohama 236, Japan; Fax: 81-45-783-2540Search for more papers by this authorKenji Okuda, Kenji Okuda Department of Bacteriology, Yokohama City University School of Medicine, Yokohama 236, Japan; Fax: 81-45-783-2540Search for more papers by this authorKenji Kosaka, Kenji Kosaka Department of Psychiatry, Yokohama City University School of Medicine, Yokohama 236, Japan; Fax: 81-45-783-2540Search for more papers by this author Chiaki Kawanishi, Corresponding Author Chiaki Kawanishi Department of Psychiatry, Yokohama City University School of Medicine, Yokohama 236, Japan; Fax: 81-45-783-2540Department of Psychiatry, Yokohama City University School of Medicine, Yokohama 236, Japan; Fax: 81-45-783-2540Search for more papers by this authorHitoshi Osaka, Hitoshi Osaka Department of Pediatrics, Yokohama City University School of Medicine, Yokohama 236, Japan; Fax: 81-45-783-2540Search for more papers by this authorKen Inoue, Ken Inoue Department of Psychiatry, Yokohama City University School of Medicine, Yokohama 236, Japan; Fax: 81-45-783-2540Search for more papers by this authorHideki Onishi, Hideki Onishi Department of Psychiatry, Yokohama City University School of Medicine, Yokohama 236, Japan; Fax: 81-45-783-2540Search for more papers by this authorYoshiteru Yamada, Yoshiteru Yamada Department of Psychiatry, Yokohama City University School of Medicine, Yokohama 236, Japan; Fax: 81-45-783-2540Search for more papers by this authorNaoya Sugiyama, Naoya Sugiyama Department of Psychiatry, Yokohama City University School of Medicine, Yokohama 236, Japan; Fax: 81-45-783-2540Search for more papers by this authorKyoko Suzuki, Kyoko Suzuki Department of Psychiatry, Yokohama City University School of Medicine, Yokohama 236, Japan; Fax: 81-45-783-2540Search for more papers by this authorTokiji Hanihara, Tokiji Hanihara Department of Psychiatry, Yokohama City University School of Medicine, Yokohama 236, Japan; Fax: 81-45-783-2540Search for more papers by this authorTomohiro Miyagawa, Tomohiro Miyagawa Department of Psychiatry, Yokohama City University School of Medicine, Yokohama 236, Japan; Fax: 81-45-783-2540Search for more papers by this authorSeiji Kimura, Seiji Kimura Department of Pediatrics, Yokohama City University School of Medicine, Yokohama 236, Japan; Fax: 81-45-783-2540 Department of Bacteriology, Yokohama City University School of Medicine, Yokohama 236, Japan; Fax: 81-45-783-2540Search for more papers by this authorSusumu Kawamoto, Susumu Kawamoto Department of Psychiatry, Yokohama City University School of Medicine, Yokohama 236, Japan; Fax: 81-45-783-2540Search for more papers by this authorKenji Okuda, Kenji Okuda Department of Bacteriology, Yokohama City University School of Medicine, Yokohama 236, Japan; Fax: 81-45-783-2540Search for more papers by this authorKenji Kosaka, Kenji Kosaka Department of Psychiatry, Yokohama City University School of Medicine, Yokohama 236, Japan; Fax: 81-45-783-2540Search for more papers by this author First published: 1995 https://doi.org/10.1002/humu.1380060214Citations: 2AboutPDF ToolsRequest permissionExport citationAdd to favoritesTrack citation ShareShare Give accessShare full text accessShare full-text accessPlease review our Terms and Conditions of Use and check box below to share full-text version of article.I have read and accept the Wiley Online Library Terms and Conditions of UseShareable LinkUse the link below to share a full-text version of this article with your friends and colleagues. Learn more.Copy URL Share a linkShare onFacebookTwitterLinked InRedditWechat No abstract is available for this article.Citing Literature Volume6, Issue21995Pages 186-187 RelatedInformation