Lamellar ichthyosis with pseudoexon activation in the transglutaminase 1 gene

We report a case of a 12‐year‐old boy who was born as a collodion baby after which thick scales developed on his entire body surface. His younger brother showed a similar skin condition. Arcuate‐shaped, large, brownish scales covered his face with ectropion. His lower legs were also covered with larger thick, brownish, plate‐like scales, but other areas were covered with smaller scales. Next‐generation sequencing for exons and splice sites detected a stop‐gain TGM1 mutation leading to p.R71* in transglutaminase 1 (TG1). Another mutation identified was a cryptic mutation in intron 3 that activated a pseudoexon, which was detected by RNA‐based analysis of hair bulbs. The deep intronic mutation caused another truncation mutation, p.N171Tfs^*45, in TG1. An in situ TG1 assay demonstrated that TG1 activity was totally lost in this case. Thus, we conclude that the severe phenotype of the patient developed due to those novel compound heterozygous null truncation mutations in TGM1.     

Pediatric case report: Clinical profile of a patient with PCWH with p.Q377X nonsense mutation in the SOX10 gene

We report the case of a Japanese patient with PCWH, a neurological variant of Waardenburg type 4. Direct sequencing of the genomic DNA obtained from peripheral leukocytes revealed the p.Q377X nonsense mutation in the SOX10 gene. The patient had mottled hypopigmented macules on the trunk since birth; such macules have not been described previously. The so‐called “white forelock”, a triangular or diamond shaped leukoderma on the forehead, was absent. We also reviewed and summarized the outcomes of 23 patients with Waardenburg syndrome type 4, PCWH and Yemenite deaf–blind hypopigmentation syndrome, in which SOX10 mutations were identified. Among them, 17 cases were reported to have hypopigmented skin macule(s). The five patients who had the white forelock had PCWH with severe neurological complications. Paradoxically, two cases had hyperpigmented spots. Heterochromia of the iris was reported in four patients.     

Geometrical Structure of Honeycomb TCP to Control Dental Pulp-Derived Cell Differentiation

Recently, dental pulp has been attracting attention as a promising source of multipotent mesenchymal stem cells (MSCs) for various clinical applications of regeneration fields. To date, we have succeeded in establishing rat dental pulp-derived cells showing the characteristics of odontoblasts under in vitro conditions. We named them Tooth matrix-forming, GFP rat-derived Cells (TGC). However, though TGC form massive dentin-like hard tissues under in vivo conditions, this does not lead to the induction of polar odontoblasts. Focusing on the importance of the geometrical structure of an artificial biomaterial to induce cell differentiation and hard tissue formation, we previously have succeeded in developing a new biomaterial, honeycomb tricalcium phosphate (TCP) scaffold with through-holes of various diameters. In this study, to induce polar odontoblasts, TGC were induced to form odontoblasts using honeycomb TCP that had various hole diameters (75, 300, and 500 μm) as a scaffold. The results showed that honeycomb TCP with 300-μm hole diameters (300TCP) differentiated TGC into polar odontoblasts that were DSP positive. Therefore, our study indicates that 300TCP is an appropriate artificial biomaterial for dentin regeneration.