No abstract

BackgroundCongenital 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 AVPR2 locus and approximately half of the Rho GTPase-activating protein 4 (ARHGAP4) 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.ARHGAP4 is expressed at high levels in hematopoietic cells, and it has been reported that an NDI patient lacking AVPR2 and all of ARHGAP4 showed immunodeficiency characterised by a marked reduction in the number of circulating CD3+ cells and almost complete absence of CD8+ cells.MethodsPCR 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.ResultsWe evaluated subjects (one child and two adults) with 11.2-kb deletion that includes the entire AVPR2 locus and approximately half of the ARHGAP4. 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 ARHGAP4 revealed that expression of RhoGAP family genes was not influenced greatly by the lack of ARHGAP4.ConclusionThese results suggest that loss of ARHGAP4 expression is not compensated for by other family members. ARHGAP4 may play some role in lymphocyte differentiation but partial loss of ARHGAP4 does not result in clinical immunodeficiency.

To clarify the clinical features of juvenile dermatomyositis (JDM) in Japanese cases, we retrospectively evaluated the characteristics of 16 children with JDM that were treated at Saitama Children's Medical Center between 1985 and 2004. The age at disease onset ranged from 3.5 to 14.1 years old (7 boys, mean age 7.9 years; 9 girls, mean age 9.2 years). In 14 patients more than two muscle enzymes were elevated at diagnosis. The antinuclear antibody at diagnosis was positive in all girls but one, while it was positive in only two boys (2/7; P<0.01). Three patients were complicated with interstitial lung disease (ILD) (18.8%) and their serum KL-6 levels were already elevated on admission. Our findings suggest that serum KL-6 levels seemed to be sensitive to the detection of ILD in an early phase, and the relatively high frequency of JDM-associated ILD indicated that a careful evaluation of the lungs was therefore required in any individuals with JDM. Of 16 patients, two boys showed a favorable improvement and prognosis without relapse for over 9 years after the termination of treatment. Overall, in girls, there is a tendency to be a delay in the diagnosis/treatment for JDM, and this disease also demonstrated a severe course.

To clarify the clinical features of juvenile dermatomyositis (JDM) in Japanese cases, we retrospectively evaluated the characteristics of 16 children with JDM that were treated at Saitama Children's Medical Center between 1985 and 2004. The age at disease onset ranged from 3.5 to 14.1 years old (7 boys, mean age 7.9 years; 9 girls, mean age 9.2 years). In 14 patients more than two muscle enzymes were elevated at diagnosis. The antinuclear antibody at diagnosis was positive in all girls but one, while it was positive in only two boys (2/7; P<0.01). Three patients were complicated with interstitial lung disease (ILD) (18.8%) and their serum KL-6 levels were already elevated on admission. Our findings suggest that serum KL-6 levels seemed to be sensitive to the detection of ILD in an early phase, and the relatively high frequency of JDM-associated ILD indicated that a careful evaluation of the lungs was therefore required in any individuals with JDM. Of 16 patients, two boys showed a favorable improvement and prognosis without relapse for over 9 years after the termination of treatment. Overall, in girls, there is a tendency to be a delay in the diagnosis/treatment for JDM, and this disease also demonstrated a severe course.

We report a CD40 ligand deficiency (CD40LD) patient who was successfully treated with unrelated cord blood transplantation (URCBT). Conditioning regimen was busulfan and cyclophosphamide. The clinical course was uneventful and durable engraftment was achieved. This successful case encourages the use of URCB as an alternative donor source for CD40LD patients.