Immunological profile in a family with nephrogenic diabetes insipidus with a novel 11 kb deletion in AVPR2 and ARHGAP4 genes

<p>Abstract</p> <p>Background</p> <p>Congenital nephrogenic diabetes insipidus (NDI) is characterised by an inability to concentrate urine despite normal or elevated plasma levels of the antidiuretic hormone arginine vasopressin. We report a Japanese extended family with NDI caused by an 11.2-kb deletion that includes the entire <it>AVPR2 </it>locus and approximately half of the <it>Rho GTPase-activating protein 4 </it>(<it>ARHGAP4</it>) locus. ARHGAP4 belongs to the RhoGAP family, Rho GTPases are critical regulators of many cellular activities, such as motility and proliferation which enhances intrinsic GTPase activity.</p> <p>ARHGAP4 is expressed at high levels in hematopoietic cells, and it has been reported that an NDI patient lacking <it>AVPR2 </it>and all of <it>ARHGAP4 </it>showed immunodeficiency characterised by a marked reduction in the number of circulating CD3+ cells and almost complete absence of CD8+ cells.</p> <p>Methods</p> <p>PCR and sequencing were performed to identify the deleted region in the Japanese NDI patients. Immunological profiles of the NDI patients were analysed by flow cytometry. We also investigated the gene expression profiles of peripheral blood mononuclear cells (PBMC) from NDI patients and healthy controls in microarray technique.</p> <p>Results</p> <p>We evaluated subjects (one child and two adults) with 11.2-kb deletion that includes the entire <it>AVPR2 </it>locus and approximately half of the <it>ARHGAP4</it>. Hematologic tests showed a reduction of CD4+ cells in one adult patient, a reduction in CD8+ cells in the paediatric patient, and a slight reduction in the serum IgG levels in the adult patients, but none of them showed susceptibility to infection. Gene expression profiling of PBMC lacking <it>ARHGAP4 </it>revealed that expression of RhoGAP family genes was not influenced greatly by the lack of <it>ARHGAP4</it>.</p> <p>Conclusion</p> <p>These results suggest that loss of <it>ARHGAP4 </it>expression is not compensated for by other family members. ARHGAP4 may play some role in lymphocyte differentiation but partial loss of <it>ARHGAP4 </it>does not result in clinical immunodeficiency.</p

Clinical features of children with nontyphoidal Salmonella bacteremia: A single institution survey in rural Japan.

Nontyphoidal Salmonella (NTS) can cause bacterial enterocolitis. Although some children with NTS infection develop bacteremia, its clinical manifestations have not been discussed adequately. Therefore, we examined children with NTS bacteremia. We retrospectively examined the medical records of 15 patients aged less than 15 years. Salmonella spp. were detected in the blood cultures of these patients between 1991 and 2014. We divided an additional sample group of 34 patients diagnosed with an NTS infection between 2005 and 2014, into 2 groups. Group bacteremia (B) included patients in whose blood cultures Salmonella spp. were detected, and group non-bacteremia (NB) included patients in whom Salmonella infection was not detected. We compared each group using Wilcoxon test and Fisher's exact test. The number of patients with fever, diarrhea, or abdominal pain was 15 (100%), 13 (87%), and 9 (60%), respectively, in the first sample of patients. However, vomiting and bloody stool were observed in only 5 patients (33%). More than 70% of patients exhibited a reduced white blood cell count, while C-reactive protein levels were variable in the patients. Salmonella spp. were detected via stool culture in 10 patients (67%). Diarrhea persisted for more than 4 days more frequently in group B than group NB (p = 0.004). The number of patients whose fever persisted for more than 4 days was significantly higher in group B than group NB (p = 0.030). Therefore, if NTS bacteremia is suspected, blood cultures should be collected and antibiotics should be initiated in cases with diarrhea or fever for more than 4 days. Furthermore, a negative stool culture result does not preclude the possibility of NTS bacteremia

A summary of the demographic and clinical characteristics of the 15 children with NTS bacteremia.

<p>A summary of the demographic and clinical characteristics of the 15 children with NTS bacteremia.</p