Two mutations of the KRT6A gene in Chinese patients with pachyonychia congenita type I / 中华医学遗传学杂志

<p><b>OBJECTIVE</b>To investigate the gene mutation in a Chinese pedigree and one sporadic case with pachyonychia congenita type I(PC-1), as well as to explore the relationship between the genotype and phenotype.</p><p><b>METHODS</b>The whole coding region of the KRT16 and KRT6A genes were amplified by long-range polymerase chain reaction (PCR). Six patients with PC-1 were studied, five of them were from a pedigree and the other one was sporadic. One unaffected member in the pedigree and 100 unrelated healthy individuals were also studied in order to exclude polymorphism. PCR products were directly sequenced to detect the mutation.</p><p><b>RESULTS</b>No mutations in the KRT16 gene were observed. All patients harbored a mutation in the KRT6A gene. All five patients in the pedigree had a mutation at codon 465 (TAC to CAC) which substitutes tyrosine (Y) by histidine (H). In the sporadic patient, codon 171 (AAC) was mutated to GAC, which changes the asparagines (N) to aspartic acid (D). No such mutations were found in the unaffected member of the pedigree and the 100 unrelated controls. The mutation of Y465H is located at the end of 2B and N171D at the beginning of 1A domain of KRT6A, both are hotspots for pathogenic keratin mutations.</p><p><b>CONCLUSION</b>The mutations Y465H and N171D of the KRT16A gene were detected in the pedigree and the sporadic case respectively. The Y465H mutation was a novel mutation, and the N171D mutation was reported recently.</p>

Effects of prenatal stress on kinetic properties of high-voltage-activated Ca2+ channel in freshly isolated offspring rat hippocampal CA3 pyramidal neurons / 南方医科大学学报

<p><b>OBJECTIVE</b>To investigate the effects of prenatal stress (PNS) on kinetic properties of high-voltage-activated (HVA) Ca(2+) channel in freshly isolated offspring rat hippocampal CA3 pyramidal neurons.</p><p><b>METHODS</b>The pregnant rats were exposed to restraint stress, and the hippocampal CA3 pyramidal neurons were freshly isolated from the offspring rats to record voltage-gate Ca(2+) channel currents in these neurons using whole-cell configuration of patch-clamp technique.</p><p><b>RESULTS</b>PNS significantly increased HVA calcium current density and integral current but did not alter the steady-state activation and steady-state inactivation properties of HVA Ca(2+) channel in the offspring rat CA3 neurons. The maximal HVA calcium current density was -40.89-/+0.31 pA/pF in the control group (n=10) and -49.44-/+0.37 pA/pF in PNS group (n=8, P<0.01). The maximal integral current of the HVA Ca(2+) channel was 106.81-/+4.20 nA*ms in the control group (n=10) and 133.49-/+2.59 nA*ms in the PNS group (n=8, P<0.01).</p><p><b>CONCLUSION</b>Maternal exposure to stress during the critical phase of pregnancy may result in long-lasting effects on the ion channels of the hippocampal neurons in the offspring rats.</p>

Gender-dependent difference of NF-kappaB expression in the hippocampus of prenatally stressed offspring rats / 生理学报

In this study, immunohistochemistry and Western blot were used to determine whether the expression of NF-kappaB in the hippocampus of prenatally stressed offspring rats is gender-dependent. The results were as follows: In the female offspring rats, the expressions of p65 in the hippocampal dentate gyrus in mid-term stress (MS) and late-term stress (LS) groups were significantly less than that in the control group (P<0.01). There was a significant difference between MS and LS groups (P<0.01). The expressions of p50 in all regions of hippocampus in MS and LS groups were significantly more than that in the control group (P<0.01). A significant difference was also present between MS and LS groups (P<0.01). In the male offspring rats, the expressions of p65 in the hippocampal dentate gyrus in MS and LS groups were evidently more than that in the control group (P<0.01). There was a significant difference between MS and LS groups (P<0.01). The expressions of p50 in all regions of hippocampus in MS and LS groups were significantly less than that in the control group (P<0.05, P<0.01). There was also a significant difference in p65 expression between MS and LS groups (P<0.01). In addition, in the control group the expressions of p65 in the hippocampal dentate gyrus of female offspring rats were significantly more than that of male ones (P<0.01). However, in LS group the expressions of p65 in the hippocampal dentate gyrus of female offspring rats were significantly less than that of male ones (P<0.01). Moreover, there was no significant difference in p65 expression between female and male offspring rats in MS group. In the control group the gender difference in the expression of p50 was only observed in hippocampal CA1 (P<0.01). The expressions of p50 in all regions of hippocampus of female offspring rats were significantly more than that of male ones in LS group (P<0.01). There was no significant difference in p50 expression between female and male offspring rats in MS group. The results of Western blot were similar to those of immunohistochemical study. These results indicate that prenatal stress in different gestational periods significantly affects the expressions of p65 and p50 in hippocampus, and this effect is gender-dependent. This may be one of the mechanisms underlying the gender difference in the ability of learning and memory of the prenatally stressed offspring rats.