含糖酸化鉄注射液の長期投与でFGF23関連低リン血症性骨軟化症を来たしたクローン病の１例

症例は50歳代，男性．クローン病で２年前に右半結腸切除術，小腸部分切除を施行．術後に他院にてアダリムマブを導入され，クローン病は臨床的寛解の状態であった．４か月前より下肢を中心とした疼痛が出現した．アダリムマブによる薬剤起因性ループスあるいは腸炎性関節炎を疑い，２か月前よりアダリムマブ投与を中止し，プレドニゾロンの内服を開始するも改善を認めなかった．血液検査にて，低リン血症と高アルカリフォスファターゼ血症を認め，精査治療目的で当院に紹介入院となった．骨塩定量検査にて骨密度の低下を，骨シンチグラフィーで疼痛を認める骨への多発取り込みを認め，骨軟化症と診断した．血清のfibroblast growth factor 23（FGF23）が175pg/ml と高値であり，入院前まで定期的に使用されていた含糖酸化鉄注射液による，FGF23関連低リン血症性骨軟化症と診断した．含糖酸化鉄注射液投与を中止し，リン製剤とビタミンD 製剤の投与を開始したところ，徐々に低リン血症と高アルカリフォスファターゼ血症の改善を認めた．その後の経過は良好で，FGF23値は徐々に低下を示し，下肢を中心とした疼痛は軽快し，退院した．長期的に含糖酸化鉄注射液を投与する場合は，FGF23関連低リン血症の早期発見のため，血中リン濃度を定期的に測定する必要がある．The case is a man in his 50s. He underwent operations of right half colon resection and small intestine segmental resection due to Crohn’s disease two years ago. After surgery, Adalimumab was introduced in other hospital, and he was a state of the clinical remission in Crohn’s disease. The sharp pain mainly on lower limbs develops from four months ago. We doubted drug origin-related lupus with Adalimumab or enteritis-related joint pain. Therefore, we stopped Adalimumab injection and started internal use of the prednisolone, however the symptoms did not improve and had continued for two months.Laboratory test showed hypophosphatemia and hyperphosphatasemia and then he was transported to our hospital. Bone mineral quantity showed bone salt decrease and bone scan showed increased uptakes in multiple bones. Fibroblast growth factor23 (FGF23) of the serum was high (175pg/ml), and we diagnosed him FGF23-mediated hypophosphatemic osteomalasia induced by prolonged administration of saccharated ferric acid.Saccharated ferric acid has regularly been used until hospitalization. After stopping the ferric acid injection, and taking phosphorus and vitamin D, hypophosphatemia and hyperphosphatasemia was gradually improved. FGF23 level gradually reduced, and the sharp pain mainly on lower limbs was relieved, and it became a discharge. Regular measurement of serum phosphorus concentration is necessary for early detection of the FGF23-related hypophosphatemia in patients with long term use of saccharated ferric acid

The Gametic Non-Lethal Gene Gal on Chromosome 5 Is Indispensable for the Transmission of the Co-Induced Semidwarfing Gene d60 in Rice

The gametic lethal gene gal in combination with the semidwarfing gene d60 causes complementary lethality in rice. Here, we attempted to ascertain the existence of gal and clarify male gamete abortion caused by d60 and gal. Through the F2 to F4 generations derived from the cross between D60gal-homozygous and d60Gal-homozygous, progenies of the partial sterile plants (D60d60Galgal) were segregated in a ratio of 1 semidwarf (1 d60d60GalGal):2 tall and quarter sterile (2 D60d60Galgal):6 tall (2 D60d60GalGal:1 D60D60GalGal:2 D60D60Galgal:1 D60D60galgal), which is skewed from the Mendelian ratio of 1 semidwarf:3 tall. However, the F4 generation was derived from fertile and tall heterozygous F2 plants (D60d60GalGal), which were segregated in the Mendelian ratio of 1[semidwarf (d60d60GalGal)]:2[1 semidwarf:3 tall (D60d60GalGal)]:1[tall (D60D60GalGal)]. The backcrossing of D60Gal-homozygous tall F4 plants with Hokuriku 100 resulted in fertile BCF1 and BCF2 segregated in a ratio of 1 semidwarf:3 tall, proving that d60 is inherited as a single recessive gene in the D60d60GalGal genetic background (i.e., in the absence of gal). Further, gal was localized on chromosome 5, which is evident from the deviated segregation of d1 as 1:8 and linkage with simple sequence repeat (SSR) markers. Next-generation sequencing identified the candidate SNP responsible for Gal. In F1 and sterile F2, at the binucleate stage, partial pollen discontinued development. Degraded pollen lost vegetative nuclei, but second pollen mitosis raising two generative nuclei was observed. Thus, our study describes a novel genetic model for a reproductive barrier. This is the first report on such a complementary lethal gene, whose mutation allows the transmission of a co-induced valuable semidwarfing gene d60

Genetic Performance of the Semidwarfing Allele sd1 Derived from a Japonica Rice Cultivar and Minimum Requirements to Detect Its Single-Nucleotide Polymorphism by MiSeq Whole-Genome Sequencing

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Isogenic Japonica Rice Koshihikari Integrated with Late Flowering Gene Hd16 and Semidwarfing Gene sd1 to Prevent High Temperature Maturation and Lodging by Typhoon

We developed semidwarf and late-maturing isogenics of Koshihikari to stabilize high yield and avoid high temperature maturation. Whole-genome analysis (WGS) was conducted to examine the transitional changes in the entire genome, the size of DNA fragments integrated with the target gene, and genes accompanying the target gene owing to the progress of backcrossing. In both Koshihikari Hd16 (BC7F4) and Koshihikari sd1Hd16 (BC8F2), an SNP from adenine to guanine was detected in Hd16 at 32,996,608 bp on chromosome 3, which is known to be a causative mutation of Hd16 in Nipponbare. In Koshihikari sd1Hd16 (BC8F2), an SNP from thymine to guanine was detected in sd1 at 38,267,510 bp on chromosome 1. From BC7 to BC8, the size of the DNA fragment integrated with Hd16 decreased by 5871 bp. Koshihikari sd1Hd16 flowered 12.1 days later than Koshishikari or Koshihikari sd1 did and was 14.2 cm (15%) shorter than Koshihikari. The yield in Koshishikari sd1Hd16 (63.2 kg/a) was 7.0% higher than that of Koshihikari. This is a new germplasm designed to avoid heat damage at ripening during high-temperature summer periods by late maturation owing to Hd16 as well as to avoid lodging by autumn typhoons by semidwarfness owing to sd1