Constructive rescue of TFIIH instability by an alternative isoform of XPD derived from a mutated XPD allele in mild but not severe XP-D/CS.

Mutations in XPD cause xeroderma pigmentosum (XP), XP and Cockayne syndrome (CS) crossover syndrome (XP/CS), trichothiodystrophy and cerebro-oculo-facio-skeletal syndrome (COFS). COFS represents the most severe end of the CS spectrum. This study reports two Japanese patients, COFS-05-135 and COFS-Chiba1, who died at ages of <1 year and exhibited typical COFS manifestations caused by XPD mutations p.[I619del];[R666W] and p.[G47R];[I619del], respectively. Two other cases of severe XP-D/CS (XP group D/CS), XP1JI (p.[G47R];[0]) and XPCS1PV (p.[R666W];[0]), died at ages <2 years. On the other hand, two cases of mild XP-D/CS, XP1NE (p.[G47R];[L461V;V716_R730del]) and XPCS118LV (p.[L461V;V716_R730del];[R666W]), lived beyond 37 years of age. p.I619Del and p.[L461V;V716_R730del] are functionally null; therefore, despite the differences in clinical manifestations, the functional protein in all of these patients was either p.G47R or p.R666W. To resolve the discrepancies in these XPD genotype-phenotype relationships, the p.[L461V;V716_R730del] allele was analyzed and we found that p.[L461V;A717G] was expressed from the same allele as p.[L461V;V716_R730del] by authentic splicing. Additionally, p.[L461V;A717G] could partially rescue the loss of XPD function, resulting in the milder manifestations observed in XP1NE and XPCS118LV.

Phase transformation of zirconia ceramics by hydrothermal degradation.

Zirconia has found wide application in dentistry because of its high mechanical strength and superior esthetic properties. However, zirconia degradation caused by phase transformation occurring in a hydrothermal environment is of concern. In the present study, phase transformation and microstructure of tetragonal zirconia polycrystal partially stabilized with yttrium oxide (Y-TZP) and alumina-toughened zirconia (ATZ) sintered at different temperatures were estimated. On grazing angle X-ray diffraction analysis, ATZ showed less phase transformation to the monoclinic phase during hydrothermal treatment and this transformation appeared to occur within a few micrometers below the surface. At a higher sintering temperature the monoclinic phase content of ATZ was found to be lesser than that of Y-TZP, indicating that the alumina in ATZ was effective in suppressing hydrothermal degradation. Examination by transmission electron microscopy and studying of electron backscatter diffraction patterns indicated that grain growth in ATZ was slightly suppressed compared with that in Y-TZP at higher sintering temperatures. The present study demonstrated the effect of adding alumina to zirconia for suppressing hydrothermal degradation and studied the effect of this addition on grain growth in zirconia.