ABSTRACT
OBJECTIVE@#To explore the clinical features and genetic basis for a patient with hereditary hypophosphatemic rickets with hypercalciuria(HHRH).@*METHODS@#Clinical data of the patient was collected. The patient was subjected to whole exome capture and next generation sequencing (NGS). Suspected variants were verified by Sanger sequencing.@*RESULTS@#The patient presented with hypophosphatemic rickets, short stature, hypercalciuria, and renal stones. NGS showed that he has carried compound heterozygous variants of the SLC34A3 gene, namely c.532_533delCA(p.Q178Vfs*6) and c.894_925+69del(splicing). His parents were asymptomatic heterozygous carriers of one of the variants. Based on ACMG guidelines, both variants were classified as pathogenic.@*CONCLUSION@#The compound heterozygous variants c.532_533delCA (p.Q178Vfs*6) and c.894_925+69del(splicing) of the SLC34A3 gene probably underlie the disease in this child. Above finding has enriched the variant spectrum for HHRH. Based on the results, prenatal diagnosis may be provided for the family.
ABSTRACT
Objective To investigate the effects of sIL-2R in plasma on regulatory T cells (Treg) in children with Kawasaki disease ( KD ) .Methods Thirty-three children with KD and fourteen age-matched healthy children were enrolled in this study .The proportions of CD4+CD25+Foxp3+Treg cells in pe-ripheral blood and mean fluorescence intensity (MFI) of phosphorylated-STAT5 (pSTAT5) protein in CD4+CD25+T cells were analyzed by flow cytometry .The concentrations of sIL-2R, IL-2, IL-7 and IL-15 in plas-ma were measured by cytometric bead array ( CBA ) .Real-time PCR was performed to detect the gene ex-pressions of Foxp3, GITR, CTLA4, IL-2Rα, IL-2Rβand IL-2Rγat mRNA level as well as the expressions of IL-17A and ROR-γt at mRNA level in CD4+CD25-T cells.Results (1) Compared with the control group, the proportions of CD4+CD25+Foxp3+Treg cells in peripheral blood from patients with KD and the expressions of associated factors including Foxp 3, GITR and CTLA-4 at mRNA level were significantly down-regulated (P0.05).(4)The expressions of IL-2Rαand IL-2Rβat mRNA level in CD4+CD25+T cells from patients with acute KD were lower than those of the healthy subjects (P0.05).The concentrations of sIL-2R in plasma were negatively correlated with the expressions of IL-2Rβand Foxp3 at mRNA level and pSTAT5 at protein level (P<0.05).The expression of pSTAT5 protein had positive correlation with the ex-pression of Foxp3 at mRNA level (P<0.05).Conclusion Aberrant IL-2/STAT5 signaling pathway media-ted by significantly increased concentration of sIL-2R in plasma might be one of the factors leading to down-regulation of Treg cells in patients with acute KD .