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Ehlers–Danlos syndrome spondylodysplastic type 3 (EDSSPD3, OMIM 612350) is an inherited recessive connective tissues disease caused by loss of function of SLC39A13/ZIP13, a zinc transporter belonging to the Slc39a/ZIP family. Patients with EDSSPD3 suffer from impaired development of bone and connective tissues, and muscular hypotonia, or myopathy. However, whether ZIP13 participates in the early differentiation process of these cell types remains unclear. In this study, we investigated the role of ZIP13 in myogenic differentiation using murine myoblast cell line (C2C12) as well as human patient-derived induced pluripotent stem cells (iPSCs). We found that ZIP13 expression was upregulated by myogenic stimulation in C2C12 cells, and its knockdown disrupted myotubular differentiation. Myocytes differentiated from iPSCs of patients with EDSSPD3 (EDSSPD3-iPSCs) exhibited incomplete myogenic differentiation. Moreover, the phenotypic abnormalities of EDSSPD3-iPSC-derived myocytes were corrected by genomic editing of the pathogenic ZIP13 mutation, suggesting the indispensable role of ZIP13 in myogenic differentiation. These results clearly indicate that ZIP13 is required for proper myogenic differentiation and that the study of EDSSPD3-iPSCs may help shed light on the molecular basis underlying various clinical features caused by the loss of ZIP13.

The purpose of the study was to evaluate the hypothesis that patients having a vasovagal reaction (VVR) after blood vessel puncture show increased FDG accumulation in bilateral adrenal glands.Over the past 8 years, 26 patients experienced a VVR after blood vessel puncture following intra-venous injection of FDG at our institution. Of the 26 patients, 16 underwent multiple-occasion FDG-PET/CT scans while suffering a VVR at only one examination. All 16 patients had no morphological abnormality in the adrenal glands on FDG-PET/CT and follow-up examination. For the 16, we retrospectively reviewed the FDG-PET/CT scan with respect to the adrenal glands and compared the result to that for the FDG-PET/CT scan of the same patient when there was no VVR event. We used both visual analysis and semi-quantitative analysis employing either maximum standardized uptake value (SUVmax) or adrenal-to-liver (A/L) SUVmax ratio.On visual analysis of the FDG-PET/CT with VVR, accumulations in both of the adrenal glands was judged positive, defined as higher than the hepatic accumulation, in 84 % of the cases. The SUVmax in the right adrenal gland was 2.79 ± 0.69 with VVR and 1.92 ± 0.33 without VVR; this value in the left adrenal gland was 3.07 ± 0.71 with VVR and 2.05 ± 0.39 without. Mean SUVmax of both adrenal glands was 2.93 ± 0.66 with VVR and 1.98 ± 0.35 without. The A/L SUVmax ratio in the right adrenal gland was 1.02 ± 0.26 with VVR and 0.69 ± 0.11 without; this value in the left was 1.11 ± 0.23 with VVR and 0.74 ± 0.15 without. The mean A/L SUVmax ratio of both adrenal glands was 1.06 ± 0.24 with VVR and 0.72 ± 0.13 without. Each parameter with VVR was significantly higher than that without. For the two adrenal glands, the mean SUVmax with VVR was 48 % higher than that without VVR.We confirmed the hypothesis that patients having a VVR after blood vessel puncture show increased FDG accumulation in their bilateral adrenal glands. This may reflect hyper-metabolism of the adrenal glands in synthesizing and secreting catecholamine.