e99078c71bbacf740871079801c46e9c pmc_29470411.pdf f5b86e7167eb1c50ce3a087598e244a6875a9736 pmc_29470411.pdf fe325579e1eaaccdb69fd4d72af48d735300eea0a7129535f36c750e41955779 pmc_29470411.pdf Title: Stroke-Like Episodes and Cerebellar Syndrome in Phosphomannomutase Deficiency (PMM2-CDG): Evidence for Hypoglycosylation-Driven Channelopathy Subject: Stroke-like episodes (SLE) occur in phosphomannomutase deficiency (PMM2-CDG), and may complicate the course of channelopathies related to Familial Hemiplegic Migraine (FHM) caused by mutations in CACNA1A (encoding CaV2.1 channel). The underlying pathomechanisms are unknown. We analyze clinical variables to detect risk factors for SLE in a series of 43 PMM2-CDG patients. We explore the hypothesis of abnormal CaV2.1 function due to aberrant N-glycosylation as a potential novel pathomechanism of SLE and ataxia in PMM2-CDG by using whole-cell patch-clamp, N-glycosylation blockade and mutagenesis. Nine SLE were identified. Neuroimages showed no signs of stroke. Comparison of characteristics between SLE positive versus negative patients’ group showed no differences. Acute and chronic phenotypes of patients with PMM2-CDG or CACNA1A channelopathies show similarities. Hypoglycosylation of both CaV2.1 subunits (1A and 2) induced gain-of-function effects on channel gating that mirrored those reported for pathogenic CACNA1A mutations linked to FHM and ataxia. Unoccupied N-glycosylation site N283 at 1A contributes to a gain-of-function by lessening CaV2.1 inactivation. Hypoglycosylation of the 2 subunit also participates in the gain-of-function effect by promoting voltage-dependent opening of the CaV2.1 channel. CaV2.1 hypoglycosylation may cause ataxia and SLEs in PMM2-CDG patients. Aberrant CaV2.1 N-glycosylation as a novel pathomechanism in PMM2-CDG opens new therapeutic possibilities. Keywords: ataxia; cerebellum; congenital disorders of glycosylation; magentic resonance Imaging (MRI); stroke-like; CaV2.1 voltage-gated calcium channel Author: Mercè Izquierdo-Serra, Antonio F. Martínez-Monseny, Laura López, Julia Carrillo-García, Albert Edo, Juan Darío Ortigoza-Escobar, Óscar García, Ramón Cancho-Candela, M Llanos Carrasco-Marina, Luis G. Gutiérrez-Solana, Daniel Cuadras, Jordi Muchart, Raquel Montero, Rafael Artuch, Celia Pérez-Cerdá, Belén Pérez, Belén Pérez-Dueñas, Alfons Macaya, José M. 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yes no 453 0 KIFKOE+PalatinoLinotype CID TrueType Identity-H yes yes yes 454 0 KIFKOF+PalatinoLinotype TrueType WinAnsi yes yes no 455 0 KIFLPP+TimesNewRoman TrueType WinAnsi yes yes no 456 0 KIFKNB+PalatinoLinotype,Italic TrueType WinAnsi yes yes no 484 0 KIFKOD+PalatinoLinotype,Bold TrueType WinAnsi yes yes no 485 0 KIFKOE+PalatinoLinotype CID TrueType Identity-H yes yes yes 486 0 KIFKOF+PalatinoLinotype TrueType WinAnsi yes yes no 487 0 KIFLPP+TimesNewRoman TrueType WinAnsi yes yes no 488 0 KIFKNB+PalatinoLinotype,Italic TrueType WinAnsi yes yes no 521 0 KIFKOD+PalatinoLinotype,Bold TrueType WinAnsi yes yes no 522 0 KIFKOE+PalatinoLinotype CID TrueType Identity-H yes yes yes 523 0 KIFKOF+PalatinoLinotype TrueType WinAnsi yes yes no 524 0 KIFLPP+TimesNewRoman TrueType WinAnsi yes yes no 525 0 ROWTUD+PazoMath Type 1 Builtin yes yes no 560 0 GIGFZE+CMR10 Type 1 Builtin yes yes no 562 0 Jhove (Rel. 1.22.1, 2019-04-17) Date: 2022-06-15 02:28:31 CEST RepresentationInformation: pmc_29470411.pdf ReportingModule: PDF-hul, Rel. 1.12.1 (2019-04-17) LastModified: 2018-03-26 03:49:41 CEST Size: 2622350 Format: PDF Version: 1.5 Status: Well-Formed and valid SignatureMatches: PDF-hul MIMEtype: application/pdf PDFMetadata: Objects: 0 FreeObjects: 3 IncrementalUpdates: 0 DocumentCatalog: ViewerPreferences: HideToolbar: false HideMenubar: false HideWindowUI: false FitWindow: true CenterWindow: false DisplayDocTitle: false NonFullScreenPageMode: UseNone Direction: L2R ViewArea: CropBox ViewClip: CropBox PrintArea: CropBox PageClip: CropBox PageLayout: SinglePage PageMode: UseNone Outlines: Item: Title: ぉのぴひはつふっぴどはのぜ〴〩਼㰠⽓ 䝯呯 䐠⡳散瑩潮⸲ Item: Title: げづびふぬぴびぜ〴〩਼㰠⽓ 䝯呯 䐠⡳畢獥捴楯渮㈮ㄩ‾㸊⡜㌷㙜㌷㝜〰こぴひはにづ〭がどにづぜ〴ぜ〰ぅばどびはつづびぜ〴〩਼㰠⽓ 䝯呯 䐠⡳畢獥捴楯渮㈮㈩‾㸊⡜㌷㙜㌷㝜〰こがぅぜ〴ぜ〰ざづひびふびぜ〴ぜ〰こがぅぜ〴ぜ〰ぎづでちぴどぶづぜ〴ぜ〰ぇひはふばぜ〴〩਼㰠⽓ 䝯呯 䐠⡳畢獥捴楯渮㈮㌩‾㸊⡜㌷㙜㌷㝜〰がどぴづひちぴふひづぜ〴ぜ〰げづぶどづぷぜ〴ぜ〰ぃはねばちひどのでぜ〴ぜ〰ぃぬどのどっちぬぜ〴ぜ〰ぐひづびづのぴちぴどはのびぜ〴ぜ〰ぢづぴぷづづのぜ〴ぜ〰ぐちぴどづのぴびぜ〴ぜ〰ぷどぴとぜ〴ぜ〰ぐきき〲〭ぃいぇぜ〴ぜ〰ちのつぜ〴ぜ〰ぐちぴどづのぴびぜ〴ぜ〰ぷどぴとぜ〴ぜ〰ぃぁぃぎぁ〱ぁぜ〴ぜ〰きふぴちぴどはのびぜ〴〩਼㰠⽓ 䝯呯 䐠⡳畢獥捴楯渮㈮㐩‾㸊⡜㌷㙜㌷㝜〰いづてどっどづのぴぜ〴ぜ〰ぎ〭ぇぬべっはびべぬちぴどはのぜ〴ぜ〰ぁぬぴづひびぜ〴ぜ〰ぃちざ〲〮〱ぜ〴ぜ〰うふのっぴどはのちぬぜ〴ぜ〰ぅへばひづびびどはの〬ぜ〴ぜ〰ぁっぴどぶちぴどはの〬ぜ〴ぜ〰ちのつぜ〴ぜ〰ぉのちっぴどぶちぴどはのぜ〴〩਼㰠⽓ 䝯呯 䐠⡳畢獥捴楯渮㈮㔩‾㸊⡜㌷㙜㌷㝜〰きふぴちぴどはのぜ〴ぜ〰はてぜ〴ぜ〰〱ぁぜ〴ぜ〰ぐはぴづのぴどちぬぜ〴ぜ〰ぇぬべっはびべぬちぴどはのぜ〴ぜ〰こどぴづぜ〴ぜ〰きどねどっびぜ〴ぜ〰ごふのどっちねべっどのぜ〴ぜ〰ぅててづっぴぜ〴ぜ〰はのぜ〴ぜ〰ぃちざ〲〮〱ぜ〴ぜ〰ぉのちっぴどぶちぴどはのぜ〴〩਼㰠⽓ 䝯呯 䐠⡳散瑩潮⸳ Children: Item: Title: こぴひはにづ〭がどにづぜ〴ぜ〰ぅばどびはつづびぜ〴〩਼㰠⽓ 䝯呯 䐠⡳畢獥捴楯渮㈮㈩‾㸊⡜㌷㙜㌷㝜〰こがぅぜ〴ぜ〰ざづひびふびぜ〴ぜ〰こがぅぜ〴ぜ〰ぎづでちぴどぶづぜ〴ぜ〰ぇひはふばぜ〴〩਼㰠⽓ 䝯呯 䐠⡳畢獥捴楯渮㈮㌩‾㸊⡜㌷㙜㌷㝜〰がどぴづひちぴふひづぜ〴ぜ〰げづぶどづぷぜ〴ぜ〰ぃはねばちひどのでぜ〴ぜ〰ぃぬどのどっちぬぜ〴ぜ〰ぐひづびづのぴちぴどはのびぜ〴ぜ〰ぢづぴぷづづのぜ〴ぜ〰ぐちぴどづのぴびぜ〴ぜ〰ぷどぴとぜ〴ぜ〰ぐきき〲〭ぃいぇぜ〴ぜ〰ちのつぜ〴ぜ〰ぐちぴどづのぴびぜ〴ぜ〰ぷどぴとぜ〴ぜ〰ぃぁぃぎぁ〱ぁぜ〴ぜ〰きふぴちぴどはのびぜ〴〩਼㰠⽓ 䝯呯 䐠⡳畢獥捴楯渮㈮㐩‾㸊⡜㌷㙜㌷㝜〰いづてどっどづのぴぜ〴ぜ〰ぎ〭ぇぬべっはびべぬちぴどはのぜ〴ぜ〰ぁぬぴづひびぜ〴ぜ〰ぃちざ〲〮〱ぜ〴ぜ〰うふのっぴどはのちぬぜ〴ぜ〰ぅへばひづびびどはの〬ぜ〴ぜ〰ぁっぴどぶちぴどはの〬ぜ〴ぜ〰ちのつぜ〴ぜ〰ぉのちっぴどぶちぴどはのぜ〴〩਼㰠⽓ 䝯呯 䐠⡳畢獥捴楯渮㈮㔩‾㸊⡜㌷㙜㌷㝜〰きふぴちぴどはのぜ〴ぜ〰はてぜ〴ぜ〰〱ぁぜ〴ぜ〰ぐはぴづのぴどちぬぜ〴ぜ〰ぇぬべっはびべぬちぴどはのぜ〴ぜ〰こどぴづぜ〴ぜ〰きどねどっびぜ〴ぜ〰ごふのどっちねべっどのぜ〴ぜ〰ぅててづっぴぜ〴ぜ〰はのぜ〴ぜ〰ぃちざ〲〮〱ぜ〴ぜ〰ぉのちっぴどぶちぴどはのぜ〴〩਼㰠⽓ 䝯呯 䐠⡳散瑩潮⸳ Item: Title: こがぅぜ〴ぜ〰ざづひびふびぜ〴ぜ〰こがぅぜ〴ぜ〰ぎづでちぴどぶづぜ〴ぜ〰ぇひはふばぜ〴〩਼㰠⽓ 䝯呯 䐠⡳畢獥捴楯渮㈮㌩‾㸊⡜㌷㙜㌷㝜〰がどぴづひちぴふひづぜ〴ぜ〰げづぶどづぷぜ〴ぜ〰ぃはねばちひどのでぜ〴ぜ〰ぃぬどのどっちぬぜ〴ぜ〰ぐひづびづのぴちぴどはのびぜ〴ぜ〰ぢづぴぷづづのぜ〴ぜ〰ぐちぴどづのぴびぜ〴ぜ〰ぷどぴとぜ〴ぜ〰ぐきき〲〭ぃいぇぜ〴ぜ〰ちのつぜ〴ぜ〰ぐちぴどづのぴびぜ〴ぜ〰ぷどぴとぜ〴ぜ〰ぃぁぃぎぁ〱ぁぜ〴ぜ〰きふぴちぴどはのびぜ〴〩਼㰠⽓ 䝯呯 䐠⡳畢獥捴楯渮㈮㐩‾㸊⡜㌷㙜㌷㝜〰いづてどっどづのぴぜ〴ぜ〰ぎ〭ぇぬべっはびべぬちぴどはのぜ〴ぜ〰ぁぬぴづひびぜ〴ぜ〰ぃちざ〲〮〱ぜ〴ぜ〰うふのっぴどはのちぬぜ〴ぜ〰ぅへばひづびびどはの〬ぜ〴ぜ〰ぁっぴどぶちぴどはの〬ぜ〴ぜ〰ちのつぜ〴ぜ〰ぉのちっぴどぶちぴどはのぜ〴〩਼㰠⽓ 䝯呯 䐠⡳畢獥捴楯渮㈮㔩‾㸊⡜㌷㙜㌷㝜〰きふぴちぴどはのぜ〴ぜ〰はてぜ〴ぜ〰〱ぁぜ〴ぜ〰ぐはぴづのぴどちぬぜ〴ぜ〰ぇぬべっはびべぬちぴどはのぜ〴ぜ〰こどぴづぜ〴ぜ〰きどねどっびぜ〴ぜ〰ごふのどっちねべっどのぜ〴ぜ〰ぅててづっぴぜ〴ぜ〰はのぜ〴ぜ〰ぃちざ〲〮〱ぜ〴ぜ〰ぉのちっぴどぶちぴどはのぜ〴〩਼㰠⽓ 䝯呯 䐠⡳散瑩潮⸳ Item: Title: がどぴづひちぴふひづぜ〴ぜ〰げづぶどづぷぜ〴ぜ〰ぃはねばちひどのでぜ〴ぜ〰ぃぬどのどっちぬぜ〴ぜ〰ぐひづびづのぴちぴどはのびぜ〴ぜ〰ぢづぴぷづづのぜ〴ぜ〰ぐちぴどづのぴびぜ〴ぜ〰ぷどぴとぜ〴ぜ〰ぐきき〲〭ぃいぇぜ〴ぜ〰ちのつぜ〴ぜ〰ぐちぴどづのぴびぜ〴ぜ〰ぷどぴとぜ〴ぜ〰ぃぁぃぎぁ〱ぁぜ〴ぜ〰きふぴちぴどはのびぜ〴〩਼㰠⽓ 䝯呯 䐠⡳畢獥捴楯渮㈮㐩‾㸊⡜㌷㙜㌷㝜〰いづてどっどづのぴぜ〴ぜ〰ぎ〭ぇぬべっはびべぬちぴどはのぜ〴ぜ〰ぁぬぴづひびぜ〴ぜ〰ぃちざ〲〮〱ぜ〴ぜ〰うふのっぴどはのちぬぜ〴ぜ〰ぅへばひづびびどはの〬ぜ〴ぜ〰ぁっぴどぶちぴどはの〬ぜ〴ぜ〰ちのつぜ〴ぜ〰ぉのちっぴどぶちぴどはのぜ〴〩਼㰠⽓ 䝯呯 䐠⡳畢獥捴楯渮㈮㔩‾㸊⡜㌷㙜㌷㝜〰きふぴちぴどはのぜ〴ぜ〰はてぜ〴ぜ〰〱ぁぜ〴ぜ〰ぐはぴづのぴどちぬぜ〴ぜ〰ぇぬべっはびべぬちぴどはのぜ〴ぜ〰こどぴづぜ〴ぜ〰きどねどっびぜ〴ぜ〰ごふのどっちねべっどのぜ〴ぜ〰ぅててづっぴぜ〴ぜ〰はのぜ〴ぜ〰ぃちざ〲〮〱ぜ〴ぜ〰ぉのちっぴどぶちぴどはのぜ〴〩਼㰠⽓ 䝯呯 䐠⡳散瑩潮⸳ Item: Title: いづてどっどづのぴぜ〴ぜ〰ぎ〭ぇぬべっはびべぬちぴどはのぜ〴ぜ〰ぁぬぴづひびぜ〴ぜ〰ぃちざ〲〮〱ぜ〴ぜ〰うふのっぴどはのちぬぜ〴ぜ〰ぅへばひづびびどはの〬ぜ〴ぜ〰ぁっぴどぶちぴどはの〬ぜ〴ぜ〰ちのつぜ〴ぜ〰ぉのちっぴどぶちぴどはのぜ〴〩਼㰠⽓ 䝯呯 䐠⡳畢獥捴楯渮㈮㔩‾㸊⡜㌷㙜㌷㝜〰きふぴちぴどはのぜ〴ぜ〰はてぜ〴ぜ〰〱ぁぜ〴ぜ〰ぐはぴづのぴどちぬぜ〴ぜ〰ぇぬべっはびべぬちぴどはのぜ〴ぜ〰こどぴづぜ〴ぜ〰きどねどっびぜ〴ぜ〰ごふのどっちねべっどのぜ〴ぜ〰ぅててづっぴぜ〴ぜ〰はのぜ〴ぜ〰ぃちざ〲〮〱ぜ〴ぜ〰ぉのちっぴどぶちぴどはのぜ〴〩਼㰠⽓ 䝯呯 䐠⡳散瑩潮⸳ Item: Title: きふぴちぴどはのぜ〴ぜ〰はてぜ〴ぜ〰〱ぁぜ〴ぜ〰ぐはぴづのぴどちぬぜ〴ぜ〰ぇぬべっはびべぬちぴどはのぜ〴ぜ〰こどぴづぜ〴ぜ〰きどねどっびぜ〴ぜ〰ごふのどっちねべっどのぜ〴ぜ〰ぅててづっぴぜ〴ぜ〰はのぜ〴ぜ〰ぃちざ〲〮〱ぜ〴ぜ〰ぉのちっぴどぶちぴどはのぜ〴〩਼㰠⽓ 䝯呯 䐠⡳散瑩潮⸳ Item: Title: きちぴづひどちぬびぜ〴ぜ〰ちのつぜ〴ぜ〰きづぴとはつびぜ〴〩਼㰠⽓ 䝯呯 䐠⡳畢獥捴楯渮㌮ㄩ‾㸊⡜㌷㙜㌷㝜〰ぐちぴどづのぴびぜ〴〩਼㰠⽓ 䝯呯 䐠⡳畢獥捴楯渮㌮㈩‾㸊⡜㌷㙜㌷㝜〰がどぴづひちぴふひづぜ〴ぜ〰げづぶどづぷぜ〴〩਼㰠⽓ 䝯呯 䐠⡳畢獥捴楯渮㌮㌩‾㸊⡜㌷㙜㌷㝜〰っいぎぁぜ〴ぜ〰ぃはのびぴひふっぴびぜ〴〩਼㰠⽓ 䝯呯 䐠⡳畢獥捴楯渮㌮㐩‾㸊⡜㌷㙜㌷㝜〰えづぴづひはぬはではふびぜ〴ぜ〰ぅへばひづびびどはのぜ〴〩਼㰠⽓ 䝯呯 䐠⡳畢獥捴楯渮㌮㔩‾㸊⡜㌷㙜㌷㝜〰ぉのとどぢどぴどはのぜ〴ぜ〰はてぜ〴ぜ〰ぎ〭ぇぬべっはびべぬちぴどはのぜ〴ぜ〰どのぜ〴ぜ〰がどぶづぜ〴ぜ〰ぃづぬぬびぜ〴ぜ〰ちのつぜ〴ぜ〰しづびぴづひのぜ〴ぜ〰あぬはぴぜ〴〩਼㰠⽓ 䝯呯 䐠⡳畢獥捴楯渮㌮㘩‾㸊⡜㌷㙜㌷㝜〰ぅぬづっぴひはばとべびどはぬはでべぜ〴〩਼㰠⽓ 䝯呯 䐠⡳畢獥捴楯渮㌮㜩‾㸊⡜㌷㙜㌷㝜〰ぅぴとどっびぜ〴ぜ〰こぴちぴづねづのぴぜ〴〩਼㰠⽓ 䝯呯 䐠⡳畢獥捴楯渮㌮㠩‾㸊⡜㌷㙜㌷㝜〰こぴちぴどびぴどっちぬぜ〴ぜ〰ぁのちぬべびどびぜ〴〩਼㰠⽓ 䝯呯 䐠⡳散瑩潮⸴ Children: Item: Title: ぐちぴどづのぴびぜ〴〩਼㰠⽓ 䝯呯 䐠⡳畢獥捴楯渮㌮㈩‾㸊⡜㌷㙜㌷㝜〰がどぴづひちぴふひづぜ〴ぜ〰げづぶどづぷぜ〴〩਼㰠⽓ 䝯呯 䐠⡳畢獥捴楯渮㌮㌩‾㸊⡜㌷㙜㌷㝜〰っいぎぁぜ〴ぜ〰ぃはのびぴひふっぴびぜ〴〩਼㰠⽓ 䝯呯 䐠⡳畢獥捴楯渮㌮㐩‾㸊⡜㌷㙜㌷㝜〰えづぴづひはぬはではふびぜ〴ぜ〰ぅへばひづびびどはのぜ〴〩਼㰠⽓ 䝯呯 䐠⡳畢獥捴楯渮㌮㔩‾㸊⡜㌷㙜㌷㝜〰ぉのとどぢどぴどはのぜ〴ぜ〰はてぜ〴ぜ〰ぎ〭ぇぬべっはびべぬちぴどはのぜ〴ぜ〰どのぜ〴ぜ〰がどぶづぜ〴ぜ〰ぃづぬぬびぜ〴ぜ〰ちのつぜ〴ぜ〰しづびぴづひのぜ〴ぜ〰あぬはぴぜ〴〩਼㰠⽓ 䝯呯 䐠⡳畢獥捴楯渮㌮㘩‾㸊⡜㌷㙜㌷㝜〰ぅぬづっぴひはばとべびどはぬはでべぜ〴〩਼㰠⽓ 䝯呯 䐠⡳畢獥捴楯渮㌮㜩‾㸊⡜㌷㙜㌷㝜〰ぅぴとどっびぜ〴ぜ〰こぴちぴづねづのぴぜ〴〩਼㰠⽓ 䝯呯 䐠⡳畢獥捴楯渮㌮㠩‾㸊⡜㌷㙜㌷㝜〰こぴちぴどびぴどっちぬぜ〴ぜ〰ぁのちぬべびどびぜ〴〩਼㰠⽓ 䝯呯 䐠⡳散瑩潮⸴ Item: Title: がどぴづひちぴふひづぜ〴ぜ〰げづぶどづぷぜ〴〩਼㰠⽓ 䝯呯 䐠⡳畢獥捴楯渮㌮㌩‾㸊⡜㌷㙜㌷㝜〰っいぎぁぜ〴ぜ〰ぃはのびぴひふっぴびぜ〴〩਼㰠⽓ 䝯呯 䐠⡳畢獥捴楯渮㌮㐩‾㸊⡜㌷㙜㌷㝜〰えづぴづひはぬはではふびぜ〴ぜ〰ぅへばひづびびどはのぜ〴〩਼㰠⽓ 䝯呯 䐠⡳畢獥捴楯渮㌮㔩‾㸊⡜㌷㙜㌷㝜〰ぉのとどぢどぴどはのぜ〴ぜ〰はてぜ〴ぜ〰ぎ〭ぇぬべっはびべぬちぴどはのぜ〴ぜ〰どのぜ〴ぜ〰がどぶづぜ〴ぜ〰ぃづぬぬびぜ〴ぜ〰ちのつぜ〴ぜ〰しづびぴづひのぜ〴ぜ〰あぬはぴぜ〴〩਼㰠⽓ 䝯呯 䐠⡳畢獥捴楯渮㌮㘩‾㸊⡜㌷㙜㌷㝜〰ぅぬづっぴひはばとべびどはぬはでべぜ〴〩਼㰠⽓ 䝯呯 䐠⡳畢獥捴楯渮㌮㜩‾㸊⡜㌷㙜㌷㝜〰ぅぴとどっびぜ〴ぜ〰こぴちぴづねづのぴぜ〴〩਼㰠⽓ 䝯呯 䐠⡳畢獥捴楯渮㌮㠩‾㸊⡜㌷㙜㌷㝜〰こぴちぴどびぴどっちぬぜ〴ぜ〰ぁのちぬべびどびぜ〴〩਼㰠⽓ 䝯呯 䐠⡳散瑩潮⸴ Item: Title: っいぎぁぜ〴ぜ〰ぃはのびぴひふっぴびぜ〴〩਼㰠⽓ 䝯呯 䐠⡳畢獥捴楯渮㌮㐩‾㸊⡜㌷㙜㌷㝜〰えづぴづひはぬはではふびぜ〴ぜ〰ぅへばひづびびどはのぜ〴〩਼㰠⽓ 䝯呯 䐠⡳畢獥捴楯渮㌮㔩‾㸊⡜㌷㙜㌷㝜〰ぉのとどぢどぴどはのぜ〴ぜ〰はてぜ〴ぜ〰ぎ〭ぇぬべっはびべぬちぴどはのぜ〴ぜ〰どのぜ〴ぜ〰がどぶづぜ〴ぜ〰ぃづぬぬびぜ〴ぜ〰ちのつぜ〴ぜ〰しづびぴづひのぜ〴ぜ〰あぬはぴぜ〴〩਼㰠⽓ 䝯呯 䐠⡳畢獥捴楯渮㌮㘩‾㸊⡜㌷㙜㌷㝜〰ぅぬづっぴひはばとべびどはぬはでべぜ〴〩਼㰠⽓ 䝯呯 䐠⡳畢獥捴楯渮㌮㜩‾㸊⡜㌷㙜㌷㝜〰ぅぴとどっびぜ〴ぜ〰こぴちぴづねづのぴぜ〴〩਼㰠⽓ 䝯呯 䐠⡳畢獥捴楯渮㌮㠩‾㸊⡜㌷㙜㌷㝜〰こぴちぴどびぴどっちぬぜ〴ぜ〰ぁのちぬべびどびぜ〴〩਼㰠⽓ 䝯呯 䐠⡳散瑩潮⸴ Item: Title: えづぴづひはぬはではふびぜ〴ぜ〰ぅへばひづびびどはのぜ〴〩਼㰠⽓ 䝯呯 䐠⡳畢獥捴楯渮㌮㔩‾㸊⡜㌷㙜㌷㝜〰ぉのとどぢどぴどはのぜ〴ぜ〰はてぜ〴ぜ〰ぎ〭ぇぬべっはびべぬちぴどはのぜ〴ぜ〰どのぜ〴ぜ〰がどぶづぜ〴ぜ〰ぃづぬぬびぜ〴ぜ〰ちのつぜ〴ぜ〰しづびぴづひのぜ〴ぜ〰あぬはぴぜ〴〩਼㰠⽓ 䝯呯 䐠⡳畢獥捴楯渮㌮㘩‾㸊⡜㌷㙜㌷㝜〰ぅぬづっぴひはばとべびどはぬはでべぜ〴〩਼㰠⽓ 䝯呯 䐠⡳畢獥捴楯渮㌮㜩‾㸊⡜㌷㙜㌷㝜〰ぅぴとどっびぜ〴ぜ〰こぴちぴづねづのぴぜ〴〩਼㰠⽓ 䝯呯 䐠⡳畢獥捴楯渮㌮㠩‾㸊⡜㌷㙜㌷㝜〰こぴちぴどびぴどっちぬぜ〴ぜ〰ぁのちぬべびどびぜ〴〩਼㰠⽓ 䝯呯 䐠⡳散瑩潮⸴ Item: Title: ぉのとどぢどぴどはのぜ〴ぜ〰はてぜ〴ぜ〰ぎ〭ぇぬべっはびべぬちぴどはのぜ〴ぜ〰どのぜ〴ぜ〰がどぶづぜ〴ぜ〰ぃづぬぬびぜ〴ぜ〰ちのつぜ〴ぜ〰しづびぴづひのぜ〴ぜ〰あぬはぴぜ〴〩਼㰠⽓ 䝯呯 䐠⡳畢獥捴楯渮㌮㘩‾㸊⡜㌷㙜㌷㝜〰ぅぬづっぴひはばとべびどはぬはでべぜ〴〩਼㰠⽓ 䝯呯 䐠⡳畢獥捴楯渮㌮㜩‾㸊⡜㌷㙜㌷㝜〰ぅぴとどっびぜ〴ぜ〰こぴちぴづねづのぴぜ〴〩਼㰠⽓ 䝯呯 䐠⡳畢獥捴楯渮㌮㠩‾㸊⡜㌷㙜㌷㝜〰こぴちぴどびぴどっちぬぜ〴ぜ〰ぁのちぬべびどびぜ〴〩਼㰠⽓ 䝯呯 䐠⡳散瑩潮⸴ Item: Title: ぅぬづっぴひはばとべびどはぬはでべぜ〴〩਼㰠⽓ 䝯呯 䐠⡳畢獥捴楯渮㌮㜩‾㸊⡜㌷㙜㌷㝜〰ぅぴとどっびぜ〴ぜ〰こぴちぴづねづのぴぜ〴〩਼㰠⽓ 䝯呯 䐠⡳畢獥捴楯渮㌮㠩‾㸊⡜㌷㙜㌷㝜〰こぴちぴどびぴどっちぬぜ〴ぜ〰ぁのちぬべびどびぜ〴〩਼㰠⽓ 䝯呯 䐠⡳散瑩潮⸴ Item: Title: ぅぴとどっびぜ〴ぜ〰こぴちぴづねづのぴぜ〴〩਼㰠⽓ 䝯呯 䐠⡳畢獥捴楯渮㌮㠩‾㸊⡜㌷㙜㌷㝜〰こぴちぴどびぴどっちぬぜ〴ぜ〰ぁのちぬべびどびぜ〴〩਼㰠⽓ 䝯呯 䐠⡳散瑩潮⸴ Item: Title: こぴちぴどびぴどっちぬぜ〴ぜ〰ぁのちぬべびどびぜ〴〩਼㰠⽓ 䝯呯 䐠⡳散瑩潮⸴ Item: Title: いどびっふびびどはのぜ〴ぜ〰ちのつぜ〴ぜ〰ぃはのっぬふびどはのびぜ〴〩਼㰠⽓ 䝯呯 䐠⡳散瑩潮⸴ Item: Title: げづてづひづのっづび Filters: FilterPipeline: FlateDecode Fonts: Type1: Font: BaseFont: 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