Objective:To clarify the genetic, clinicopathologic, and neuroimaging characteristics of patients with hereditary diffuse leukoencephalopathy with spheroids (HDLS) with the colony stimulating factor 1 receptor (CSF-1R) mutation.Methods:We performed molecular genetic analysis of CSF-1R in patients with HDLS. Detailed clinical and neuroimaging findings were retrospectively investigated. Five patients were examined neuropathologically.Results:We found 6 different CSF-1R mutations in 7 index patients from unrelated Japanese families. The CSF-1R mutations included 3 novel mutations and 1 known missense mutation at evolutionarily conserved amino acids, and 1 novel splice-site mutation. We identified a novel frameshift mutation. Reverse transcription PCR analysis revealed that the frameshift mutation causes nonsense-mediated mRNA decay by generating a premature stop codon, suggesting that haploinsufficiency of CSF-1R is sufficient to cause HDLS. Western blot analysis revealed that the expression level of CSF-1R in the brain from the patients was lower than from control subjects. The characteristic MRI findings were the involvement of the white matter and thinning of the corpus callosum with signal alteration, and sequential analysis revealed that the white matter lesions and cerebral atrophy relentlessly progressed with disease duration. Spotty calcifications in the white matter were frequently observed by CT. Neuropathologic analysis revealed that microglia in the brains of the patients demonstrated distinct morphology and distribution.Conclusions:These findings suggest that patients with HDLS, irrespective of mutation type in CSF-1R, show characteristic clinical and neuroimaging features, and that perturbation of CSF-1R signaling by haploinsufficiency may play a role in microglial dysfunction leading to the pathogenesis of HDLS.

Our crystalline In–Ga–Zn oxide (IGZO) thin film has a c‐axis‐aligned crystal (CAAC) structure and maintains crystallinity even on an amorphous base layer. Although the crystal has c‐axis alignment, its a‐axis and b‐axis have random arrangement; moreover, a clear grain boundary is not observed. We fabricated a back‐channel‐etched thin‐film transistor (TFT) using the CAAC‐IGZO film. Using the CAAC‐IGZO film, more stable TFT characteristics, even with a short channel length, can be obtained, and the instability of the back channel, which is one of the biggest problems of IGZO TFTs, is solved. As a result, we improved the process of manufacturing back‐channel‐etched TFTs.

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We report, in this paper, that crystalline In–Ga–Zn-oxide (IGZO) can be formed over an amorphous surface or over an uneven surface by a sputtering process at lower than 500 °C through the purification of IGZO. Crystalline IGZO, in which no clear grain boundary is observed, shows c-axis alignment but random a- and b-axis orientations without alignment. This crystal morphology differs from other morphologies that have been known thus far, such as single crystal and polycrystal morphologies. Our model for understanding the formation of this crystal morphology [c-axis-aligned crystal (CAAC)] is also discussed. Upon thermal annealing of a deposited film at lower than 500 °C, nanocrystal regions remaining in the CAAC can be converted into the CAAC structure. Accordingly, I off can be at the yA/µm (10−24 A/µm) level at 85 °C. It has been proven that by utilizing normally-off characteristics even with L/W = 40 nm/40 nm (actual size: L/W = 68 nm/34 nm), the fabrication of a three-dimensional (3D) LSI with a 3D oxide semiconductor/Si hybrid structure is feasible.

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